Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells.
The neuropeptide Substance P (SP) is an important mediator of neuroimmunomodulatory activity. The aim of this study is to elucidate the mechanism used by SP to promote increased production of pro-inflammatory cytokines in fresh isolated rat peritoneal mast cells (rPMC). We have demonstrated that SP induces production of interleukin-6 (IL-6) in rPMC through the PI-3K, p42/44 and p38 MAP kinase pathways. SP-stimulated rPMC also exhibited an enhanced nuclear translocation of the nuclear factor kappa B (NF kappa B). The tumour necrosis factor-alpha (TNF-alpha) and IL-6 production was completely inhibited by using (E)-4-hydroxynonenal (HNE) as an inhibitor of I kappa B-alpha and -beta phosphorylation. Further, TNF-alpha and IL-6 expression was significantly inhibited by the oligonucleotides (ODNs) containing the NF kappa B element (NF kappa B decoy ODNs) but not by the scrambled control ODNs. These findings indicate that the NF kappa B pathway is involved in the transcriptional regulation of the TNF-alpha and IL-6 overexpression in primary SP-stimulated mast cells.
Azzolina
Antonina
A
Istituto di Biomedicina e Immunologia Molecolare Alberto Monroy C.N.R., Via Ugo La Malfa 153, 90146 Palermo, Italy.
Bongiovanni
Antonella
A
Lampiasi
Nadia
N
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D013373:Substance P / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P