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-kappaB.

Abstract

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-kappaB 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-kappaB but not P38 MAPK, JNK or PI3K/Akt signal pathways.

• Authors: Fu-Chen Huang
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2009 Pg. 103890 ( 2009) ISSN: 1466-1861 [Electronic] United States
• PMID: 20204057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Enzyme Inhibitors
• I-kappa B Proteins
• IL6 protein, human
• Inflammation Mediators
• Interleukin-6
• N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
• NF-kappa B
• NFKBIA protein, human
• Phenanthrenes
• Poly(ADP-ribose) Polymerase Inhibitors
• NF-KappaB Inhibitor alpha
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Active Transport, Cell Nucleus (drug effects)
• Base Sequence
• Caco-2 Cells
• DNA Primers (genetics)
• Enterocytes (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• I-kappa B Proteins (metabolism)
• Inflammation Mediators (metabolism)
• Interleukin-6 (biosynthesis, genetics)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Phenanthrenes (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerase Inhibitors
• Proto-Oncogene Proteins c-akt (metabolism)
• Salmonella (pathogenicity)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)