Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide inhibit the MEKK1/MEK4/JNK signaling pathway in LPS-stimulated macrophages
作者： Mario Delgado , Doina Ganea
DOI: 10.1016/S0165-5728(00)00359-3
关键词:
摘要: The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase activating polypeptide (PACAP), two immunomodulatory neuropeptides that affect both innate acquired immunity, downregulate TNFα expression in LPS-stimulated peritoneal macrophages Raw 264.7 cells. We showed previously VIP/PACAP change composition of CRE-binding complex promoter from highc-Jun/lowCREB, characteristic for macrophages, to lowc-Jun/highCREB, unstimulated In present study we examined effects on MEKK1/MEK4/JNK transduction pathway, subsequent changes Jun family members. Our studies indicate inhibit MEKK1 activity, phosphorylation MEK4, JNK, c-Jun. Treatment with VIP or PACAP results a decrease AP-1 binding, marked complexes c-Jun/c-Fos JunB/c-Fos. Western blots confirm stimulates JunB production macrophages. Both inhibition leading reduction phosphorylated c-Jun, stimulation JunB, are mediated through specific VPAC1 receptor cAMP/PKA pathway. interference stress-induced SAPK/JNK pathway stimulated may represent significant element regulation inflammatory response by endogenous neuropeptides.
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