Substance P Selectively Activates TNF-α Gene Expression in Murine Mast Cells

John C. Ansel*, Jeffrey R. Brown, Donald G. Payan, Melissa A. Brown

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

309 Scopus citations


There is increasing evidence that the neurologic system is capable of modulating a wide range of immunologic responses, including certain inflammatory processes in the lung, gastrointestinal tract, and skin. It has been proposed that secreted neuropeptides such as substance P (SP) may mediate these neuroinflammatory interactions by binding to and stimulating immune cells such as mast cells and lymphoid cells. SP is secreted in a variety of tissues by an extensive network of neurosensory C and A5 fibers in response to a wide range of noxious stimuli and injury. Previous studies to examine the effect of SP on mast cells have focused on its role in triggering histamine release and mediating immediate hypersensitivity responses. Recently it was demonstrated that mast cells are also capable of secreting multiple cytokines including TNF-α, IL-1, IL-3, IL-4, IL-6, and GM-CSF. In this study we tested the possibility that SP may also influence mast cell- mediated late inflammatory events by modulating the production of one or several of these cytokines. Our results indicate that SP induces TNF-α mRNA expression and TNF-α secretion in a dose-dependent manner in a murine mast cell line, CFTL 12. Likewise, SP stimulates TNF-α secretion in freshly isolated murine peritoneal mast cells. The induction of mast cell TNF-α is selective, since SP does not stimulate the production of IL-1, 1L-3, IL-4, 1L-6, or GM-CSF in these cells. The CFTL 12 mast cell line constitutively expresses high levels of SP receptor mRNA which is not modulated by PMA/cycloheximide treatment or SP. These results further support the concept that the neurologic system modulates inflammatory events by neuropeptide-mediated mast cell cytokine release.

Original languageEnglish (US)
Pages (from-to)4478-4485
Number of pages8
JournalJournal of Immunology
Issue number10
StatePublished - May 15 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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