Substance P induces TNF-α and IL-6 production through NFκB in peritoneal mast cells

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Abstract

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 κ B (NFκB). The tumour necrosis factor-α (TNF-α) and IL-6 production was completely inhibited by using (E)-4-hydroxynonenal (HNE) as an inhibitor of IκB-α and -β phosphorylation. Further, TNF-α and IL-6 expression was significantly inhibited by the oligonucleotides (ODNs) containing the NFκB element (NFκB decoy ODNs) but not by the scrambled control ODNs. These findings indicate that the NFκB pathway is involved in the transcriptional regulation of the TNF-α and IL-6 overexpression in primary SP-stimulated mast cells.

Keywords

Mast cell
TNF-α
IL-6
SP
MAPK
NFκB
ODN decoy

Abbreviations

SP
Substance P
IL-6
interleukin-6
rPMC
rat peritoneal mast cells
NFκB
nuclear factor κ B
HNE
(E)-4-hydroxynonenal
TNF-α
tumour necrosis factor-α
ODN
oligonucleotide
BMMCs
bone marrow-derived mast cells

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