Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis.
Sodium-butyrate-pretreated and Con A-stimulated P815 mast cell line generated 3T3 fibroblast proliferating activity. This fibroblast stimulatory activity was partially abrogated by three different substance P antagonists such as spantide (NK1 antagonist), FK224 (NK1 and NK2 antagonist) or FK888 (NK1 antagonist) or anti-substance P antibody. In addition to P815 mastocytoma cell, IL3-dependent, bone marrow-derived mast cells also generated fibroblast proliferating activity which was also partially abrogated by substance P antagonists. Anti-fibrogenic cytokine antibodies also inhibited mast cell-derived fibroblast proliferating activity. Substance P or histamine augmented fibrogenic cytokine-induced fibroblast proliferation which indicates that mast cell-derived histamine or substance P play an important role in induction of tissue fibrosis in fibrosing diseases.
Katayama
I
I
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, Japan.
Nishioka
K
K
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D005355:Fibrosis / Q000209:etiology; D006632:Histamine / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016207:Cytokines; D009479:Neuropeptides; D013373:Substance P; D006632:Histamine