Effect of pirfenidone on induction of chemokines in rat hepatocytes.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggest that PFD inhibits the production of CINC and MIP-2 by IL-1beta at a posttranscriptional step in hepatocytes.
Kaibori
M
M
Department of Surgery, Kansai Medical University, Osaka, Japan. kaibori@takii.kmu.ac.jp
Yanagida
H
H
Yokoigawa
N
N
Kwon
A-H
AH
Okumura
T
T
Kamiyama
Y
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics; D007700:Kinetics; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D011728:Pyridones; C093844:pirfenidone