| Autor: |
Evani SJ; Division of Combat Wound Repair, U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Building 3610, JBSA Fort Sam Houston, San Antonio, TX, 78234-7767, USA., Karna SLR; Division of Combat Wound Repair, U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Building 3610, JBSA Fort Sam Houston, San Antonio, TX, 78234-7767, USA., Seshu J; South Texas Center for Emerging Infectious Diseases (STCEID) and Department of Biology, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, USA., Leung KP; Division of Combat Wound Repair, U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Building 3610, JBSA Fort Sam Houston, San Antonio, TX, 78234-7767, USA. kai.p.leung.civ@mail.mil. |
| Abstrakt: |
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. |
