interleukin-8 and pirfenidone

Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK

Topics: Acetates; Acetylcysteine; Aminopyridines; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Benzamides; Bronchi; Cell Line; Cyclopropanes; Dapsone; Dexamethasone; Dose-Response Relationship, Drug; Epithelial Cells; Fluoroquinolones; Humans; Interleukin-1alpha; Interleukin-8; MAP Kinase Signaling System; Moxifloxacin; Neutrophils; Phosphorylation; Pyridones; Quinolines; Sulfides; Theophylline; Treatment Outcome

Hepatic ischemia-reperfusion results in a neutrophil-dependent liver injury. The process of neutrophil recruitment and activation in this injury is at least partially dependent on the induction of chemokines, such as cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) in rats. In the liver, parenchymal cells (hepatocytes), in addition to nonparenchymal cells such as Kupffer cells, have been reported to produce chemokines in the regulation of hepatic inflammation. Pirfenidone (PFD) is a new experimental drug used as an antifibrotic agent. Studies were performed to determine whether PFD influences the production of CINC and MIP-2 stimulated by interleukin (IL)-1beta in a primary culture model of rat hepatocytes.. Primary cultures of rat hepatocytes were treated with IL-1beta in the presence and absence of PFD. The protein and mRNA of CINC and MIP-2 were analyzed using enzyme-linked immunosorbent assays and Northern blots.. IL-1beta increased the release of CINC and MIP-2 into culture media in a dose- and time-dependent manner. PFD inhibited both CINC and MIP-2 release in dose-dependent fashion. However, PFD had no effect on the levels of CINC mRNA induced by IL-1beta.. These results suggest that PFD inhibits the production of CINC and MIP-2 by IL-1beta at a posttranscriptional step in hepatocytes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Chemokine CXCL2; Chemokines; Chemokines, CXC; Hepatocytes; Intercellular Signaling Peptides and Proteins; Interleukin-1; Interleukin-8; Kinetics; Pyridones; Rats