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Cutting edge: hemokinin has substance P-like function and expression in inflammation.

Abstract
Substance P (SP) belongs to the tachykinin family of molecules. SP, cleaved from preprotachykinin A, is a neuropeptide and a proinflammatory leukocyte product. SP engages neurokinin 1 receptor (NK-1R) to stimulate cells. Hemokinin (HK) is another tachykinin that binds NK-1R. HK comes from preprotachykinin C, which is distinct from preprotachykinin A. We determined whether HK functions like SP at inflammatory sites. Preprotachykinin C mRNA was in murine schistosome granulomas and intestinal lamina propria mononuclear cells. Granuloma T cells and macrophages expressed preprotachykinin C mRNA. HK bound granuloma T cell NK-1R with high affinity. SP and HK stimulated IFN-gamma production with equal potency. NK-1R antagonist blocked the effect of SP and HK on IFN-gamma secretion. Thus, both HK and SP are expressed at sites of chronic inflammation and share cell origin, receptor, and immunoregulatory function. Two distinct but functionally overlapping tachykinins govern inflammation through NK-1R at sites of chronic inflammation.
AuthorsAhmed Metwali, Arthur M Blum, David E Elliott, Tommy Setiawan, Joel V Weinstock
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 11 Pg. 6528-32 (Jun 01 2004) ISSN: 0022-1767 [Print] United States
PMID15153465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Protein Precursors
  • Receptors, Neurokinin-1
  • Tac4 protein, mouse
  • Tachykinins
  • preprotachykinin
  • Substance P
  • Interferon-gamma
Topics
  • Animals
  • Cell Line
  • Inflammation (metabolism)
  • Interferon-gamma (biosynthesis)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Protein Precursors (genetics, physiology)
  • Receptors, Neurokinin-1 (metabolism)
  • Substance P (physiology)
  • Tachykinins (genetics, physiology)

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