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 ge nerated 3T3 fibroblast proliferating activity. This fibroblast stimula tory activity was partially abrogated by three different substance P a ntagonists such as spantide (NK1 antagonist), FK224 (NK1 and NK2 antag onist) or FK888 (NK1 antagonist) or anti-substance P antibody. In addi tion 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 cytok ine antibodies also inhibited mast cell-derived fibroblast proliferati ng activity. Substance P or histamine augmented fibrogenic cytokine-in duced fibroblast proliferation which indicates that mast cell-derived histamine or substance P play an important role in induction of tissue fibrosis in fibrosing diseases. (C) 1997 Elsevier Science Ireland Ltd .