Neutrophil migration towards C5a and CXCL8 is prevented by non-steroidal anti-inflammatory drugs via inhibition of different pathways.

摘要: Background and Purpose Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to induce PG-independent actions. Here, we investigated the role of three different NSAIDs (naproxen, ibuprofen oxaprozin) on neutrophil responses CXCL8 C5a. Experimental Approach Human neutrophils were isolated from healthy volunteers by dextran Ficoll-Hypaque density gradients. Neutrophils pre-incubated with concentrations (1–100 µM) or kinase inhibitors. Neutrophil degranulation into supernatants was tested elisa zymography. chemotaxis determined using Boyden chambers. F-actin polymerization Alexa-Fluor 488-conjugated phalloidin fluorescent assay. Integrin expression assessed flow cytometry. The phosphorylation intracellular kinases studied Western blot. Key Results Pretreatment did not affect degranulation, but inhibited migration F-actin, in response C5a. Pretreatment prevented C5a-induced integrin (CD11b) up-regulation, while only reduced CXCL8-induced CD11b up-regulation. Pre-incubation naproxen oxaprozin, ibuprofen, PI3K/Akt-dependent chemotactic pathways. Both endogenous (released cell supernatants) exogenous (added cultures) PGE2 C5a- activities. Short-term incubation release. Conclusion Implications Treatment via mechanisms. Inhibition associated down-regulation, oxaprozin blocked PI3K/Akt pathway. NSAID actions independent COX inhibition release.