Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis

J Dermatol Sci. 1997 Sep;15(3):201-6. doi: 10.1016/s0923-1811(97)00608-7.


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.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Division / drug effects
  • Cell Line
  • Cytokines / pharmacology*
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects*
  • Fibrosis / etiology
  • Histamine / pharmacology
  • Mast Cells / drug effects
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neuropeptides / physiology
  • Substance P / antagonists & inhibitors
  • Substance P / pharmacology*


  • Cytokines
  • Neuropeptides
  • Substance P
  • Histamine