Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2009, Article ID 103890, 7 pages
Research Article

Upregulation of Salmonella-Induced IL-6 Production in Caco-2 Cells by PJ-34, PARP-1 Inhibitor: Involvement of PI3K, p38 MAPK, ERK, JNK, and NF- B

Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, 123, Ta-pei Road, Niao-sung Hsiang, Kaohsiung Hsien 833, Taiwan

Received 29 July 2009; Revised 14 November 2009; Accepted 14 November 2009

Academic Editor: Vera L. Petricevich

Copyright © 2009 Fu-Chen Huang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Following Salmonella invasion, intestinal epithelial cells release a distinct array of proinflammatory cytokines. Interleukin (IL)-6 produced by enterocytes may have anti-inflammatory and cell-protective effects, and may counteract some of the injurious effects of sepsis and endotoxemia. Recent studies in a variety of rodent models of experimental colitis by using PJ-34, a potent poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, support the concept that the marked beneficial effect of PJ-34 can be exploited to treat human inflammatory diseases. The present study was to investigate the effect of PJ-34 on Salmonella-induced enterocyte IL-6 production and its mechanisms. We found that PJ-34 enhanced Salmonella-induced IL-6 production in Caco-2 cells, either secreted protein or mRNA expression. PJ-34 treatment enhanced the activity of NF- B in Salmonella-infected Caco-2 cells. Besides, the involvement of PJ-34 in up-regulating IL-6 production in S. typhimurium-infected Caco-2 cells might be also through the ERK but not p38 MAPK, JNK or PI3K/Akt pathways, as demonstrated by Western blot of phosphorylated ERK, p38, JNK and Akt proteins. It suggests that PJ-34 may exert its protective effect on intestinal epithelial cells against invasive Salmonella infection by up-regulating IL-6 production through ERK and NF- B but not P38 MAPK, JNK or PI3K/Akt signal pathways.