Substance P diminishes lipopolysaccharide and interferon-gamma-induced TGF-beta 1 production by cultured murine macrophages.
Recent evidence has demonstrated the importance of substance P and its receptor in macrophage-mediated inflammatory responses. While previous studies have shown that substance P can augment proinflammatory monokine production, little is known about the effects of this neuropeptide on the production of monokines that might limit inflammation. In the present study we have investigated the effect of substance P treatment on the production of transforming growth factor-beta 1 (TGF-beta 1) in cultured murine macrophages. We report that, while substance P agonist alone elicited increases in TGF-beta 1 mRNA expression and modest increases in TGF-beta 1 secretion, substance P dramatically diminished LPS- or IFN-gamma-induced TGF-beta 1 production. These results suggest a previously unrecognized mechanism where substance P may act as a proinflammatory mediator by limiting the production of excessive levels of TGF-beta 1 by LPS- or IFN-gamma-activated macrophages.
Marriott
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Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Bost
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D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D007249:Inflammation / Q000209:etiology; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013373:Substance P / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D015850:Interleukin-6; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C065446:spantide II; C068032:GR 73632; D013373:Substance P; D007371:Interferon-gamma