Neutrophilic Inflammation: Molecular Mechanisms and Drug Discovery

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 3080

Special Issue Editors

Department of Medical Research, E-Da Hospital, Kaohsiung 824410, Taiwan
Interests: Inflammation pharmacology; Drug discovery; Cancer biology
Special Issues, Collections and Topics in MDPI journals
Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei 11031, Taiwan
Interests: natural products chemistry; mass spectrometry-based metabolomics; pharmacognosy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue "Neutrophilic Inflammation: Molecular Mechanisms and Drug Discovery" aims to provide a comprehensive overview of the molecular mechanisms underlying neutrophilic inflammation, as well as the current state of drug discovery efforts targeting this process. Neutrophilic inflammation plays a critical role in the pathogenesis of various diseases, including acute respiratory distress syndrome, chronic obstructive pulmonary disease sepsis, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, and cancer. The Special Issue will cover a broad range of topics, including neutrophil recruitment and activation, signaling pathways, the role of neutrophils in tissue damage and repair, and the development of novel therapeutic strategies. The ultimate goal is to promote a better understanding of the complex biology of neutrophilic inflammation and to facilitate the identification of new drug targets for treating inflammatory diseases. The Issue welcomes original research articles, reviews, and perspectives that cover any aspect of neutrophilic inflammation and drug discovery.

Dr. Po-Jen Chen
Dr. Kuei-Hung Lai
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neutrophilic inflammation
  • molecular mechanisms
  • drug discovery
  • neutrophil activation
  • signaling pathways
  • therapeutic strategies
  • inflammatory and autoimmune diseases
  • drug targets

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

19 pages, 4111 KiB  
Article
MARCKS Inhibition Alters Bovine Neutrophil Responses to Salmonella Typhimurium
Biomedicines 2024, 12(2), 442; https://doi.org/10.3390/biomedicines12020442 - 16 Feb 2024
Viewed by 469
Abstract
Neutrophils are innate immune cells that respond quickly to sites of bacterial infection and play an essential role in host defense. Interestingly, some bacterial pathogens benefit from exuberant neutrophil inflammation. Salmonella is one such pathogen that can utilize the toxic mediators released by [...] Read more.
Neutrophils are innate immune cells that respond quickly to sites of bacterial infection and play an essential role in host defense. Interestingly, some bacterial pathogens benefit from exuberant neutrophil inflammation. Salmonella is one such pathogen that can utilize the toxic mediators released by neutrophils to colonize the intestine and cause enterocolitis. Because neutrophils can aid gut colonization during Salmonella infection, neutrophils represent a potential host-directed therapeutic target. Myristoylated alanine-rich C-kinase substrate (MARCKS) is an actin-binding protein that plays an essential role in many neutrophil effector responses. We hypothesized that inhibition of MARCKS protein would alter bovine neutrophil responses to Salmonella Typhimurium (STm) ex vivo. We used a MARCKS inhibitor peptide to investigate the role of MARCKS in neutrophil responses to STm. This study demonstrates that MARCKS inhibition attenuated STm-induced neutrophil adhesion and chemotaxis. Interestingly, MARCKS inhibition also enhanced neutrophil phagocytosis and respiratory burst in response to STm. This is the first report describing the role of MARCKS protein in neutrophil antibacterial responses. Full article
(This article belongs to the Special Issue Neutrophilic Inflammation: Molecular Mechanisms and Drug Discovery)
Show Figures

Figure 1

20 pages, 4663 KiB  
Article
C-Terminal Region of Caveolin-3 Contains a Stretch of Amino Acid Residues Capable of Diminishing Symptoms of Experimental Autoimmune Encephalomyelitis but Not Rheumatoid Arthritis Modeled in Rats
Biomedicines 2023, 11(10), 2855; https://doi.org/10.3390/biomedicines11102855 - 21 Oct 2023
Viewed by 1129
Abstract
A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure–function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3’s ability to reduce [...] Read more.
A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure–function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3’s ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC50 = 0.42 μM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague–Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model. Full article
(This article belongs to the Special Issue Neutrophilic Inflammation: Molecular Mechanisms and Drug Discovery)
Show Figures

Figure 1

14 pages, 2217 KiB  
Article
Detailed Mechanisms Underlying Neutrophil Bactericidal Activity against Streptococcus pneumoniae
Biomedicines 2023, 11(8), 2252; https://doi.org/10.3390/biomedicines11082252 - 11 Aug 2023
Viewed by 1085
Abstract
Neutrophils are an essential cellular component of innate immunity and control bacterial infections through a combination of intracellular and extracellular killing methods. Although the importance of neutrophils has been established, the exact methods used to handle particular bacterial challenges and the efficiency of [...] Read more.
Neutrophils are an essential cellular component of innate immunity and control bacterial infections through a combination of intracellular and extracellular killing methods. Although the importance of neutrophils has been established, the exact methods used to handle particular bacterial challenges and the efficiency of bacterial killing remain not well understood. In this study, we addressed how neutrophils eliminate Streptococcus pneumoniae (Spn), a leading cause of community acquired and post-influenza bacterial pneumonia. We analyzed killing methods with variable bacterial:neutrophil concentrations and following priming with PAM3CSK4 (P3CSK), an agonist for Toll-like-receptor 2 (TLR2). Our results show that murine neutrophils display surprisingly weak bactericidal activity against Spn, employing a predominantly extracellular mode of killing at lower concentrations of bacteria, whereas challenges with higher bacterial numbers induce both extracellular and intracellular elimination modes but require TLR2 activation. TLR2 activation increased reactive oxygen species (ROS) and neutrophil extracellular trap (NET) formation in response to Spn. Despite this, supernatants from P3CSK-stimulated neutrophils failed to independently alter bacterial replication. Our study reveals that unstimulated neutrophils are capable of eliminating bacteria only at lower concentrations via extracellular killing methods, whereas TLR2 activation primes neutrophil-mediated killing using both intracellular and extracellular methods under higher bacterial burdens. Full article
(This article belongs to the Special Issue Neutrophilic Inflammation: Molecular Mechanisms and Drug Discovery)
Show Figures

Figure 1

Back to TopTop