Involvement of p38 and JNK MAPKs pathways in Substance P-induced production of TNF-alpha by peritoneal mast cells.
Mast cells play a central role in both inflammation and immediate allergic reactions. We have previously shown that Substance P (SP) stimulates TNF-alpha mRNA and protein expression in rat peritoneal mast cells (PMC). In the present paper, we investigated whether the induction of TNF-alpha 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-alpha production. The highly specific p38 MAPK inhibitor SB203580 and the blocker of PI-3K wortmannin, abolished SP-induced increase in TNF-alpha 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-alpha expression 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.
Azzolina
Antonina
A
Istituto di Biologia dello Sviluppo C.N.R., via Ugo La Malfa 153, Palermo, Italia.
Guarneri
Patrizia
P
Lampiasi
Nadia
N
D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases
D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases