Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many studies have shown that tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation. Neuropeptide substance P (SP) has been known to exert significant influence on production of certain inflammatory cytokine by immune cells. Immunopathogenic mechanism underlying the effect of neuropeptide substance P (SP) and the specific amino acid sequence of SP that induces TNF has not been clearly studied. Employing ex vivo and in vitro model systems, we investigated the direct effect of different sequences of SP on TNF secretion by whole blood and separated total mononuclear cells. Aliquots of blood samples (1 ml) or Ficoll-Hypaque-separated total mononuclear cells (1 x 10(6)/ml) were cultured with different concentrations of SP and its sequences (SP 1-4, SP 4-11) or vasoactive intestinal peptide (VIP) for 24 hr at 37 degrees C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF-sensitive WEHI 164 subclone 13 cell line. Plasma from blood samples or lymphocytes treated with whole SP and SP 4-11 at 10(-7), 10(-8), and 10(-9) M concentrations induced significant production of TNF compared to negligible levels of TNF produced by SP 1-4-treated and untreated cultures. VIP at all concentrations tested did not induce TNF production and was similar to untreated control cultures. Separated mononuclear cells also produced significant levels of TNF in response to SP and SP 4-11. Anti-TNF-alpha antibodies neutralized the TNF induced by SP 4-11 in plasma. These studies suggest that an ex vivo system using whole blood may be an ideal model to study the effects of SP on TNF production. These studies also demonstrated that the TNF inducing activity of SP residues in the region containing amino acids 4 to 11.
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PMID:Substance P induces tumor necrosis factor in an ex vivo model system. 749 30

Substance P has various immunomodulatory effects, including in vitro modification of lymphocyte proliferation and cytokine release. Elevated levels of substance P and increased staining of substance P-positive nerve fibres have been reported in atopic dermatitis patients. We examined fluoresceinated substance P binding to a range of lymphocyte subsets and compared the results in atopic dermatitis, non-atopic psoriasis patients and normal controls. Fluoresceinated substance P and phycoerythrin-labelled monoclonal antibodies to CD3, CD4, CD8, CD57, CD19 and CD14 were incubated in duplicate with Ficoll-Hypaque separated peripheral blood mononuclear leukocytes. With flow cytometry the fluoresceinated substance P-positive cells were identifiable as a peak of positively fluorescent cells, and the percentages of positive cells were measured. We have demonstrated binding of fluoresceinated substance P to all subsets examined, with significantly less binding to atopic dermatitis CD3-, CD8- and CD57-positive cells. This may affect cytokine release and hence be important in the pathogenesis of atopic dermatitis.
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PMID:Substance P binding to peripheral blood mononuclear leukocytes in atopic dermatitis. 922 14