Editorial

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4 pages, 216 KiB

Open AccessEditorial

Metabolic Inflammation and Cellular Immunity

by Sardar Sindhu and Rasheed Ahmad

Cells 2023, 12(12), 1615; https://doi.org/10.3390/cells12121615 - 13 Jun 2023

Viewed by 907

Abstract

Metabolic and immune cell responses are intimately linked and cross-regulated [...] Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

Research

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19 pages, 929 KiB

Open AccessArticle

Genetic Variations in IL-1β, TNF-α, and TGF-β Associated with the Severity of Chronic Cervical Spondylitis in Patients

by Shashi Ranjan Mani Yadav, Bela Goyal, Garima Mamgain, Ashish Kothari, Sandeep Kumar, Sarama Saha, Manisha Naithani, Anissa Atif Mirza, Raj Kumar and Rajnish Arora

Cells 2023, 12(12), 1594; https://doi.org/10.3390/cells12121594 - 09 Jun 2023

Cited by 2 | Viewed by 1490

Abstract

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated [...] Read more.

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated the SNPs and allelic distribution of the three most prevalent cytokines genes, IL-1β (-511C/T), TNF-α (-308G/A), and TGF-β (-509C/T), along with serum levels of these cytokines in 252 subjects. SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and digested fragments were separated and visualized using agarose gel electrophoresis and Native Polyacrylamide gel electrophoresis (PAGE). The serum cytokine levels were analyzed with a flow cytometer using a customized multiplex bead-based assay. It was observed that these SNPs did not reflect the susceptibility to CCS but were associated with susceptibility to CCS. We found a significant association between the C/C and G/G genotypes and the C and G alleles of IL-1β and TNF-α, respectively, suggesting a lower risk of CCS. The frequency distribution of risk alleles (-511T) and (-308A) were simultaneously higher in CCS compared to the control, reflecting the susceptibility to CCS. TGF-β showed a significant association with disease susceptibility, along with a significant correlation between age and the chronicity of CCS. The serum cytokine levels were significantly different in CCS and controls. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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23 pages, 9467 KiB

Open AccessArticle

Timing of Interleukin-4 Stimulation of Macrophages Determines Their Anti-Microbial Activity during Infection with Salmonella enterica Serovar Typhimurium

by Natascha Brigo, Emely Neumaier, Christa Pfeifhofer-Obermair, Philipp Grubwieser, Sabine Engl, Sylvia Berger, Markus Seifert, Vera Reinstadler, Herbert Oberacher and Günter Weiss

Cells 2023, 12(8), 1164; https://doi.org/10.3390/cells12081164 - 14 Apr 2023

Cited by 1 | Viewed by 1695

Abstract

Priming of macrophages with interferon-gamma (IFNγ) or interleukin-4 (IL-4) leads to polarisation into pro-inflammatory or anti-inflammatory subtypes, which produce key enzymes such as inducible nitric oxide synthase (iNOS) and arginase 1 (ARG1), respectively, and in this way determine host responses to infection. Importantly, [...] Read more.

Priming of macrophages with interferon-gamma (IFNγ) or interleukin-4 (IL-4) leads to polarisation into pro-inflammatory or anti-inflammatory subtypes, which produce key enzymes such as inducible nitric oxide synthase (iNOS) and arginase 1 (ARG1), respectively, and in this way determine host responses to infection. Importantly, L-arginine is the substrate for both enzymes. ARG1 upregulation is associated with increased pathogen load in different infection models. However, while differentiation of macrophages with IL-4 impairs host resistance to the intracellular bacterium Salmonella enterica serovar Typhimurium (S.tm), little is known on the effects of IL-4 on unpolarised macrophages during infection. Therefore, bone-marrow-derived macrophages (BMDM) from C57BL/6N, Tie2Cre^+/−ARG1^fl/fl (KO), Tie2Cre^−/−ARG1^fl/fl (WT) mice were infected with S.tm in the undifferentiated state and then stimulated with IL-4 or IFNγ. In addition, BMDM of C57BL/6N mice were first polarised upon stimulation with IL-4 or IFNγ and then infected with S.tm. Interestingly, in contrast to polarisation of BMDM with IL-4 prior to infection, treatment of non-polarised S.tm-infected BMDM with IL-4 resulted in improved infection control whereas stimulation with IFNγ led to an increase in intracellular bacterial numbers compared to unstimulated controls. This effect of IL-4 was paralleled by decreased ARG1 levels and increased iNOS expression. Furthermore, the L-arginine pathway metabolites ornithine and polyamines were enriched in unpolarised cells infected with S.tm and stimulated with IL-4. Depletion of L-arginine reversed the protective effect of IL-4 toward infection control. Our data show that stimulation of S.tm-infected macrophages with IL-4 reduced bacterial multiplication via metabolic re-programming of L-arginine-dependent pathways. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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16 pages, 29974 KiB

Open AccessArticle

Increased Adipose Tissue Expression of IL-23 Associates with Inflammatory Markers in People with High LDL Cholesterol

by Shihab Kochumon, Amal Hasan, Fatema Al-Rashed, Sardar Sindhu, Reeby Thomas, Texy Jacob, Amnah Al-Sayyar, Hossein Arefanian, Ashraf Al Madhoun, Ebaa Al-Ozairi, Fawaz Alzaid, Heikki A. Koistinen, Fahd Al-Mulla, Jaakko Tuomilehto and Rasheed Ahmad

Cells 2022, 11(19), 3072; https://doi.org/10.3390/cells11193072 - 29 Sep 2022

Cited by 9 | Viewed by 2020

Abstract

Chronic low-grade inflammation induced by obesity is a central risk factor for the development of metabolic syndrome. High low-density lipoprotein cholesterol (LDL-c) induces inflammation, which is a common denominator in metabolic syndrome. IL-23 plays a significant role in the pathogenesis of meta-inflammatory diseases; [...] Read more.

Chronic low-grade inflammation induced by obesity is a central risk factor for the development of metabolic syndrome. High low-density lipoprotein cholesterol (LDL-c) induces inflammation, which is a common denominator in metabolic syndrome. IL-23 plays a significant role in the pathogenesis of meta-inflammatory diseases; however, its relationship with LDL-c remains elusive. In this cross-sectional study, we determined whether the adipose tissue IL-23 expression was associated with other inflammatory mediators in people with increased plasma LDL-c concentrations. Subcutaneous adipose tissue biopsies were collected from 60 people, sub-divided into two groups based on their plasma LDL-c concentrations (<2.9 and ≥2.9 mmol/L). Adipose expression of IL-23 and inflammatory markers were determined using real-time qRT-PCR; plasma concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and LDL-c were determined using the standard method; and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Adipose IL-23 transcripts were found to be increased in people with high LDL-c, compared to low LDL-c group (H-LDL-c: 1.63 ± 0.10–Fold; L-LDL-c: 1.27 ± 0.09–Fold; p < 0.01); IL-23 correlated positively with LDL-c (r = 0.471, p < 0.0001). Immunochemistry analysis showed that AT IL-23 protein expression was also elevated in the people with H-LDL-c. IL-23 expression in the high LDL-c group was associated with multiple adipose inflammatory biomarkers (p ≤ 0.05), including macrophage markers (CD11c, CD68, CD86, CD127), TLRs (TLR8, TLR10), IRF3, pro-inflammatory cytokines (TNF-α, IL-12, IL-18), and chemokines (CXCL8, CCL3, CCL5, CCL15, CCL20). Notably, in this cohort, IL-23 expression correlated inversely with plasma adiponectin. In conclusion, adipose IL-23 may be an inflammatory biomarker for disease progression in people with high LDL-c. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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15 pages, 2739 KiB

Open AccessArticle

SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients

by Mohammed J. A. Haider, Zahraa Albaqsumi, Fahd Al-Mulla, Rasheed Ahmad and Fatema Al-Rashed

Cells 2022, 11(17), 2670; https://doi.org/10.3390/cells11172670 - 28 Aug 2022

Cited by 4 | Viewed by 1783

Abstract

The C-type lectin receptors (CLRs) Dectin-1 and Dectin-2 are involved in several innate immune responses and are expressed mainly in dendritic cells, monocytes, and macrophages. Dectin-1 activation exacerbates obesity, inflammation, and insulin resistance/type 2 diabetes (T2D). However, the role of Dectin-2 is not [...] Read more.

The C-type lectin receptors (CLRs) Dectin-1 and Dectin-2 are involved in several innate immune responses and are expressed mainly in dendritic cells, monocytes, and macrophages. Dectin-1 activation exacerbates obesity, inflammation, and insulin resistance/type 2 diabetes (T2D). However, the role of Dectin-2 is not clear in T2D. This study aims to evaluate the expression and function of Dectin-2 in peripheral blood mononuclear cells (PBMCs) isolated from diabetic patients and non-diabetic controls. Flow-cytometry and qRT-PCR were performed to evaluate the expression of Dectin-2 in different leukocyte subpopulations isolated from T2D patients (n = 10) and matched non-diabetic controls (n = 11). The functional activity of Dectin-2 was identified in PBMCs. CRP, IL-1β, and TNF-α concentrations were determined by ELISA. siRNA transfection and Western blotting were performed to assess p-Syk and p-NF-kB expression. siRNA transfection was performed to knock down the gene of interest. Our results show that Dectin-2 expression was the highest in monocytes compared with other leukocyte subpopulations. The expression of Dectin-2 was significantly increased in the monocytes of T2D patients compared with non-diabetic controls. Dectin-2 expression positively correlated with markers of glucose homeostasis, including HOMA-IR and HbA1c. The expression of inflammatory markers was elevated in the PBMCs of T2D patients. Interestingly, SOCS3, a negative regulator of inflammation, was expressed significantly lowlier in the PBMCs of T2D patients. Moreover, SOCS3 expression was negatively correlated with Dectin-2 expression level. The further analysis of inflammatory signaling pathways showed a persistent activation of the Dectin-2-Syk-NFkB pathway that was instigated by the diminished expression of SOCS3. Dectin-2 activation failed to induce SOCS3 expression and suppress subsequent inflammatory responses in the PBMCs of diabetic patients. siRNA-mediated knockdown of SOCS3 in PBMCs displayed a similar inflammatory phenotype to diabetic PBMCs when exposed to Dectin-2 ligands. Altogether, our findings suggest that elevated Dectin-2 and its relationship with SOCS3 could be involved in the abnormal immune response observed in T2D patients. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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10 pages, 642 KiB

Open AccessArticle

Expression of Caspase-3 in Circulating Innate Lymphoid Cells Subtypes Is Altered by Treatment with Metformin and Fluvastatin in High-Fat Diet Fed C57BL/6 Mice

by Vuyolwethu Mxinwa, Bongani B. Nkambule, Tawanda M. Nyambuya and Phiwayinkosi V. Dludla

Cells 2022, 11(9), 1430; https://doi.org/10.3390/cells11091430 - 23 Apr 2022

Cited by 3 | Viewed by 1802

Abstract

The current study aimed to determine the expression levels of caspase-3 in circulating innate lymphoid cell subtypes (ILCs) in a high-fat diet (HFD)-induced prediabetes mouse model. Another critical point was to assess the therapeutic effects of metformin and fluvastatin in modulating caspase-3 activation [...] Read more.

The current study aimed to determine the expression levels of caspase-3 in circulating innate lymphoid cell subtypes (ILCs) in a high-fat diet (HFD)-induced prediabetes mouse model. Another critical point was to assess the therapeutic effects of metformin and fluvastatin in modulating caspase-3 activation in ILCs within these HFD-fed mice. Prominent results showed that mice exposed to HFD for 14 weeks displayed impaired glucose tolerance that was accompanied by elevated levels of low-density lipoprotein cholesterol (LDL-c) and altered haematological profile as characterised by significantly increased concentrations of red blood cell count, white cell count and lymphocytes when compared to those fed a low-fat diet (LFD). Moreover, the expression of caspase-3 in ILC1 and ILC3 was significantly increased in the HFD groups in comparison to the LFD-fed group. Notably, six-week treatment with metformin and fluvastatin reduced the caspase-3 activation in ILC subtypes. The reduced caspase-3 activation in ILC1 was inversely associated with HDL-c levels following metformin treatment. Interestingly, the reduced caspase-3 activation in ILC3 was associated with lower total cholesterol following fluvastatin treatment in these HFD-fed mice. However, there were no differences in activation of caspase-3 on ILC2 or any association between caspase-3 activation and changes in body weight or fasting blood glucose. Thus, while HFD-feeding clearly modulates ILCs, potentially leading to pro-apoptotic mechanisms, metformin and fluvastatin may play a major role in protecting against such metabolic disturbances. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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19 pages, 7036 KiB

Open AccessArticle

Pregnant Women and Endocrine Disruptors: Role of P2X7 Receptor and Mitochondrial Alterations in Placental Cell Disorders

by Sophie Fouyet, Elodie Olivier, Pascale Leproux, Mélody Dutot and Patrice Rat

Cells 2022, 11(3), 495; https://doi.org/10.3390/cells11030495 - 31 Jan 2022

Cited by 11 | Viewed by 2751

Abstract

In pregnant women, the lungs, skin and placenta are exposed daily to endocrine-disrupting chemicals (EDCs). EDCs induce multiple adverse effects, not only on endocrine organs, but also on non-endocrine organs, with the P2X7 cell death receptor being potentially the common key element. Our [...] Read more.

In pregnant women, the lungs, skin and placenta are exposed daily to endocrine-disrupting chemicals (EDCs). EDCs induce multiple adverse effects, not only on endocrine organs, but also on non-endocrine organs, with the P2X7 cell death receptor being potentially the common key element. Our objective was first to investigate mechanisms of EDCs toxicity in both endocrine and non-endocrine cells through P2X7 receptor activation, and second, to compare the level of activation in lung, skin and placental cells. In addition, apoptosis in placental cells was studied because the placenta is the most exposed organ to EDCs and has essential endocrine functions. A total of nine EDCs were evaluated on three human cell models. We observed that the P2X7 receptor was not activated by EDCs in lung non-endocrine cells but was activated in skin and placenta cells, with the highest activation in placenta cells. P2X7 receptor activation and apoptosis are pathways shared by all tested EDCs in endocrine placental cells. P2X7 receptor activation along with apoptosis induction could be key elements in understanding endocrine placental and skin disorders induced by EDCs. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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14 pages, 3101 KiB

Open AccessFeature PaperArticle

Saliva Metabolomics in Dry Mouth Patients with Head and Neck Cancer or Sjögren’s Syndrome

by Håvard Hynne, Elise Mørk Sandås, Katja Benedikte Prestø Elgstøen, Helge Rootwelt, Tor P. Utheim, Hilde Kanli Galtung and Janicke Liaaen Jensen

Cells 2022, 11(3), 323; https://doi.org/10.3390/cells11030323 - 19 Jan 2022

Cited by 13 | Viewed by 2556

Abstract

The etiology of dry mouth conditions is multi-faceted. Patients radiated after head and neck cancer (HNC) and those with primary Sjögren’s syndrome (pSS) share many of the same symptoms despite different causes. With the aim of better understanding the pathophysiology and biochemical processes [...] Read more.

The etiology of dry mouth conditions is multi-faceted. Patients radiated after head and neck cancer (HNC) and those with primary Sjögren’s syndrome (pSS) share many of the same symptoms despite different causes. With the aim of better understanding the pathophysiology and biochemical processes behind dry mouth with different etiologies, we investigated the metabolic profile of 10 HNC patients, 9 pSS patients and 10 healthy controls using high-performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) metabolomics. Principal component analysis (PCA) revealed different metabolic profiles when comparing all subjects included in the study. Both patient groups showed higher ratios of several pyrimidine nucleotides and nucleosides when compared to controls. This finding may indicate that purinergic signaling plays a role in dry mouth conditions. Moreover, significantly increased levels of DL-3-aminoisobutyric acid were found in HNC patients when compared to controls, and a similar tendency was observed in the pSS patients. Furthermore, a dysregulation in amino acid metabolism was observed in both patient groups. In conclusion, metabolomics analysis showed separate metabolic profiles for HNC and pSS patients as compared to controls that could be useful in diagnostics and for elucidating the different pathophysiologies. The demonstrated dysregulation of pyrimidine nucleotides and levels of metabolites derived from amino acids in the patient groups should be studied further. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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16 pages, 3188 KiB

Open AccessArticle

Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines

by Ertan Küçüksayan, Anna Sansone, Chryssostomos Chatgilialoglu, Tomris Ozben, Demet Tekeli, Günel Talibova and Carla Ferreri

Cells 2022, 11(2), 225; https://doi.org/10.3390/cells11020225 - 11 Jan 2022

Cited by 10 | Viewed by 2845

Abstract

The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association [...] Read more.

The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 μM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triple-negative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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Review

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22 pages, 2250 KiB

Open AccessReview

Neutrophil Extracellular Traps in Asthma: Friends or Foes?

by Remo Poto, Mohamed Shamji, Gianni Marone, Stephen R. Durham, Guy W. Scadding and Gilda Varricchi

Cells 2022, 11(21), 3521; https://doi.org/10.3390/cells11213521 - 07 Nov 2022

Cited by 7 | Viewed by 3825

Abstract

Asthma is a chronic inflammatory disease characterized by variable airflow limitation and airway hyperresponsiveness. A plethora of immune and structural cells are involved in asthma pathogenesis. The roles of neutrophils and their mediators in different asthma phenotypes are largely unknown. Neutrophil extracellular traps [...] Read more.

Asthma is a chronic inflammatory disease characterized by variable airflow limitation and airway hyperresponsiveness. A plethora of immune and structural cells are involved in asthma pathogenesis. The roles of neutrophils and their mediators in different asthma phenotypes are largely unknown. Neutrophil extracellular traps (NETs) are net-like structures composed of DNA scaffolds, histones and granular proteins released by activated neutrophils. NETs were originally described as a process to entrap and kill a variety of microorganisms. NET formation can be achieved through a cell-death process, termed NETosis, or in association with the release of DNA from viable neutrophils. NETs can also promote the resolution of inflammation by degrading cytokines and chemokines. NETs have been implicated in the pathogenesis of various non-infectious conditions, including autoimmunity, cancer and even allergic disorders. Putative surrogate NET biomarkers (e.g., double-strand DNA (dsDNA), myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (CitH3)) have been found in different sites/fluids of patients with asthma. Targeting NETs has been proposed as a therapeutic strategy in several diseases. However, different NETs and NET components may have alternate, even opposite, consequences on inflammation. Here we review recent findings emphasizing the pathogenic and therapeutic potential of NETs in asthma. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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18 pages, 720 KiB

Open AccessReview

The Clinical Chameleon of Autoinflammatory Diseases in Children

by Eugenio Sangiorgi and Donato Rigante

Cells 2022, 11(14), 2231; https://doi.org/10.3390/cells11142231 - 18 Jul 2022

Cited by 17 | Viewed by 2938

Abstract

The very first line of defense in humans is innate immunity, serving as a critical strongpoint in the regulation of inflammation. Abnormalities of the innate immunity machinery make up a motley group of rare diseases, named ‘autoinflammatory’, which are caused by mutations in [...] Read more.

The very first line of defense in humans is innate immunity, serving as a critical strongpoint in the regulation of inflammation. Abnormalities of the innate immunity machinery make up a motley group of rare diseases, named ‘autoinflammatory’, which are caused by mutations in genes involved in different immune pathways. Self-limited inflammatory bouts involving skin, serosal membranes, joints, gut and other districts of the human body burst and recur with variable periodicity in most autoinflammatory diseases (ADs), often leading to secondary amyloidosis as a long-term complication. Dysregulated inflammasome activity, overproduction of interleukin (IL)-1 or other IL-1-related cytokines and delayed shutdown of inflammation are pivotal keys in the majority of ADs. The recent progress of cellular biology has clarified many molecular mechanisms behind monogenic ADs, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome (or ‘autosomal dominant familial periodic fever’), cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, hereditary pyogenic diseases, idiopathic granulomatous diseases and defects of the ubiquitin-proteasome pathway. A long-lasting history of recurrent fevers should require the ruling out of chronic infections and malignancies before considering ADs in children. Little is known about the potential origin of polygenic ADs, in which sterile cytokine-mediated inflammation results from the activation of the innate immunity network, without familial recurrency, such as periodic fever/aphthous stomatitis/pharyngitis/cervical adenopathy (PFAPA) syndrome. The puzzle of febrile attacks recurring over time with chameleonic multi-inflammatory symptoms in children demands the inspection of the mixture of clinical data, inflammation parameters in the different disease phases, assessment of therapeutic efficacy of a handful of drugs such as corticosteroids, colchicine or IL-1 antagonists, and genotype analysis to exclude or confirm a monogenic origin. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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16 pages, 2410 KiB

Open AccessReview

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

by Miguel A. Bermúdez, Laura Pereira, Cristina Fraile, Laura Valerio, María A. Balboa and Jesús Balsinde

Cells 2022, 11(14), 2146; https://doi.org/10.3390/cells11142146 - 08 Jul 2022

Cited by 16 | Viewed by 4268

Abstract

In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 [...] Read more.

In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial β-oxidation of oleic acid. In this review, we discuss the current knowledge of the effects of palmitoleic acid and, where available, sapienic acid and hypogeic acid, on metabolic diseases such as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and cancer. The results have shown diverse effects among studies in cell lines, animal models and humans. Palmitoleic acid was described as a lipokine able to regulate different metabolic processes such as an increase in insulin sensitivity in muscle, β cell proliferation, prevention of endoplasmic reticulum stress and lipogenic activity in white adipocytes. Numerous beneficial effects have been attributed to palmitoleic acid, both in mouse models and in cell lines. However, its role in humans is not fully understood, and is sometimes controversial. Regarding sapienic acid and hypogeic acid, studies on their biological effects are still scarce, but accumulating evidence suggests that they also play important roles in metabolic regulation. The multiplicity of effects reported for palmitoleic acid and the compartmentalized manner in which they often occur, may suggest the overlapping actions of multiple isomers being present at the same or neighboring locations. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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17 pages, 731 KiB

Open AccessReview

Extracellular Vesicles from Adipose Tissue Could Promote Metabolic Adaptation through PI3K/Akt/mTOR

by Jaime Delgadillo-Velázquez, Herminia Mendivil-Alvarado, Carlos Daniel Coronado-Alvarado and Humberto Astiazaran-Garcia

Cells 2022, 11(11), 1831; https://doi.org/10.3390/cells11111831 - 03 Jun 2022

Cited by 5 | Viewed by 2707

Abstract

Extracellular vesicles (EVs) are nanoparticles secreted by cells under physiological and pathological conditions, such as metabolic diseases. In this context, EVs are considered potential key mediators in the physiopathology of obesity. It has been reported that EVs derived from adipose tissue (ADEVs) contribute [...] Read more.

Extracellular vesicles (EVs) are nanoparticles secreted by cells under physiological and pathological conditions, such as metabolic diseases. In this context, EVs are considered potential key mediators in the physiopathology of obesity. It has been reported that EVs derived from adipose tissue (ADEVs) contribute to the development of a local inflammatory response that leads to adipose tissue dysfunction. In addition, it has been proposed that EVs are associated with the onset and progression of several obesity-related metabolic diseases such as insulin resistance. In particular, characterizing the molecular fingerprint of obesity-related ADEVs can provide a bigger picture that better reflects metabolic adaptation though PI3K/Akt/mTOR. Hence, in this review we describe the possible crosstalk communication of ADEVs with metabolically active organs and the intracellular response in the insulin signaling pathway. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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21 pages, 2525 KiB

Open AccessFeature PaperReview

Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

by Daniil Shevyrev, Valeriy Tereshchenko, Vladimir Kozlov and Sergey Sennikov

Cells 2022, 11(2), 194; https://doi.org/10.3390/cells11020194 - 07 Jan 2022

Cited by 10 | Viewed by 2986

Abstract

It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of [...] Read more.

It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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18 pages, 3844 KiB

Open AccessReview

The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints

by Sandra Haupt, Tobias Niedrist, Harald Sourij, Stephan Schwarzinger and Othmar Moser

Cells 2022, 11(1), 153; https://doi.org/10.3390/cells11010153 - 04 Jan 2022

Cited by 6 | Viewed by 6387

Abstract

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological [...] Read more.

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can be used as biological age predictors which are able to detect excessive acceleration or deceleration of aging. Analytical methods examining aging are often not suitable, expensive, time-consuming or require a high level of technical expertise. Therefore, research focusses on combining analytical methods which have the potential to simultaneously analyse epigenetic, genomic as well as metabolic changes. Full article

(This article belongs to the Special Issue Metabolic Inflammation and Cellular Immunity)

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