INVOLVEMENT OF p38 AND JNK MAPKs PATHWAYS IN SUBSTANCE P-INDUCED PRODUCTION OF TNF-α BY PERITONEAL MAST CELLS

Author： Azzolina A. Guarneri P. Lampiasi N.

ISSN： 1043-4666

Source： Cytokine, Vol.18, Iss.2, 2002-04, pp. : 72-80

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Abstract

Mast cells play a central role in both inflammation and immediate allergic reactions. We have previously shown that Substance P (SP) stimulates TNF-α mRNA and protein expression in rat peritoneal mast cells (PMC). In the present paper, we investigated whether the induction of TNF-α production by the mast cells agonist involves MAPKs signalling pathways. We found that as early as 5 min after PMC exposure to SP, phosphorylation of p38 MAPK and JNK was induced. On the contrary, phosphorylation of p42/44 MAPK occurred only after a 30 min exposure to SP and did not correlate with SP-induced TNF-α production. The highly specific p38 MAPK inhibitor SB203580 and the blocker of PI-3K wortmannin, abolished SP-induced increase in TNF-α mRNA and protein levels and showed to reduce the SP-mediated histamine secretion. In addition, wortmannin reduced SP-mediated JNK phosphorylation. The results reveal that the induction of TNF-αexpression and histamine exocytosis by exposure of rat PMC to substance P requires the activation of p38 and JNK MAPKs pathways. Moreover, they suggest PI-3K as a possible upstream component of JNK pathway in SP-induced inflammatory reactions. .