PMID- 10580796 OWN - NLM STAT- MEDLINE DCOM- 19991209 LR - 20190826 IS - 0165-5728 (Print) IS - 0165-5728 (Linking) VI - 101 IP - 2 DP - 1999 Nov 15 TI - Mast cell production of TNF-alpha induced by substance P evidence for a modulatory role of substance P-antagonists. PG - 128-36 AB - Unregulated increasing of Tumor necrosis factor-alpha (TNF-alpha) could be pathogenic in inflammatory diseases. The aim of this study was to investigate the anti-inflammatory role of the Substance P-antagonists (SPAs) through the inhibition of histamine release (HR) and TNF-alpha production from mast cell. Rat peritoneal mast cells (PMC) stimulated with Substance P (SP), in the presence of SPAs or not, were analyzed for HR and TNF-alpha protein production. Competitive Polymerase Chain Reaction, with an internal standard competing with target cDNA for the same primers, was used to determine the TNF-alpha mRNA expression. We show that the increase of either HR and TNF-alpha levels in peritoneal (PMC) after induction with SP was inhibited by pre-incubation with SPA or with the Peptide 101 (P101), while the [D-Pro2, D-Phe7, D-Trp9]-SP (dSP) had no effect. Neuraminidase treatment suggests that dSP, as well as SP, interacts with sialic acid residues on the cell surface. Moreover, SPA and P101 also inhibit the release of histamine and TNF-alpha induced by dSP suggesting that a receptor-independent mechanism is involved. These data could be useful to better understand the mechanisms involved in the mast cell activation and TNF-alpha production in the inflammatory diseases where SP is involved. FAU - Cocchiara, R AU - Cocchiara R AD - Istituto di Biologia dello Sviluppo, CNR, Palermo, Italy. FAU - Lampiasi, N AU - Lampiasi N FAU - Albeggiani, G AU - Albeggiani G FAU - Bongiovanni, A AU - Bongiovanni A FAU - Azzolina, A AU - Azzolina A FAU - Geraci, D AU - Geraci D LA - eng PT - Journal Article PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 33507-63-0 (Substance P) RN - EC 3.2.1.18 (Neuraminidase) SB - IM MH - Animals MH - Female MH - Histamine Release/drug effects MH - Mast Cells/*drug effects/metabolism MH - Neuraminidase/pharmacology MH - Polymerase Chain Reaction MH - RNA, Messenger/analysis MH - Rats MH - Rats, Wistar MH - Substance P/*antagonists & inhibitors/*pharmacology MH - Tumor Necrosis Factor-alpha/*biosynthesis/genetics EDAT- 1999/12/02 09:00 MHDA- 2000/06/01 09:00 CRDT- 1999/12/02 09:00 PHST- 1999/12/02 09:00 [pubmed] PHST- 2000/06/01 09:00 [medline] PHST- 1999/12/02 09:00 [entrez] AID - S0165572899001381 [pii] AID - 10.1016/s0165-5728(99)00138-1 [doi] PST - ppublish SO - J Neuroimmunol. 1999 Nov 15;101(2):128-36. doi: 10.1016/s0165-5728(99)00138-1.