Pirfenidone regulates LPS mediated activation of neutrophils
Autor: | Shankar J. Evani, Kai P. Leung, Janakiram Seshu, S. L. Rajasekhar Karna |
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Rok vydání: | 2020 |
Předmět: |
Lipopolysaccharides
0301 basic medicine Cell biology Chemokine Neutrophils Pyridones Phagocytosis lcsh:Medicine Inflammation Drug action Article Neutrophil Activation 03 medical and health sciences 0302 clinical medicine medicine Humans lcsh:Science Multidisciplinary Innate immune system biology business.industry Chemotaxis Anti-Inflammatory Agents Non-Steroidal lcsh:R Pirfenidone Mechanisms of disease 030104 developmental biology Immunology Neutrophil degranulation biology.protein Cytokines lcsh:Q medicine.symptom business Signal Transduction 030215 immunology medicine.drug |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue inflammation and damage. Drugs with anti-inflammatory and anti-fibrotic effects are of promise for improving healing by balancing the primary defensive functions and excessive tissue damage actions. Of interest, pirfenidone (Pf), an FDA approved anti-fibrotic drug to treat idiopathic pulmonary fibrosis, has been shown to ameliorate inflammation in several animal models including mouse deep partial-thickness burn wounds. However, there is a lack of mechanistic insights into Pf drug action on inflammatory cells such as neutrophils. Here, we examined the treatment effects of Pf on LPS-stimulated neutrophils as a model of non-sterile inflammation. Firstly, Pf reduced chemotaxis and production of pro-inflammatory ROS, cytokines, and chemokines by LPS-activated neutrophils. Secondly, Pf increased anti-inflammatory IL-1RA and reduced neutrophil degranulation, phagocytosis, and NETosis. Thirdly, Pf affected downstream signaling kinases which might directly or indirectly influence neutrophil responses to LPS. In conclusion, the results suggest that Pf lessens the inflammatory phenotypes of LPS-activated neutrophils. |
Databáze: | OpenAIRE |
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