Role of mitogen-activated protein kinases in the iNOS production and cytokine secretion by Salmonella enterica serovar Typhimurium porins

The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both physiological and pathological functions. The present study examined the role of mitogen-activated protein kinases (MAPKs) in the regulation of iNOS and proinflammatory cytokine production in RAW 264.7 cells in res...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2008-03, Vol.41 (3), p.279-285
Main Authors: Vitiello, Mariateresa, D’Isanto, Marina, Finamore, Emiliana, Ciarcia, Roberto, Kampanaraki, Aikaterini, Galdiero, Marilena
Format: Article
Language:English
Subjects:
Animals
Anthracenes - pharmacology
Cytokine
Cytokines - metabolism
Imidazoles - pharmacology
iNOS
Macrophage Activation
Macrophages - drug effects
Macrophages - enzymology
MAPKs
Mice
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - physiology
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - metabolism
Porins
Porins - metabolism
Porins - pharmacology
Protein Kinase Inhibitors - pharmacology
Pyridines - pharmacology
Salmonella enterica
Salmonella typhimurium
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Summary:The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both physiological and pathological functions. The present study examined the role of mitogen-activated protein kinases (MAPKs) in the regulation of iNOS and proinflammatory cytokine production in RAW 264.7 cells in response to Salmonella enterica serovar Typhimurium porins. By use of Western blotting for iNOS detection and enzyme-linked immunosorbent assay (ELISA) for quantization of cytokine secretion, selective pharmacological inhibitors of MAPK pathways were tested for dissecting the molecular mechanisms underlying the mediation of these signaling in porins-stimulated murine macrophages. S. enterica serovar Typhimurium porins activated iNOS expression, NO production and interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) release. Treatment of cells with SB203580 and SP600125 (inhibitors of p38 and JNK, respectively) significantly affected porin-stimulated iNOS and NO production. Concomitant decrease in the proinflammatory cytokine secretion was detected. These data confirm the importance of the MAPKs cascade in macrophage activation by bacterial product opening up new strategies for therapy of septic shock.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2007.11.021