Cutting edge: hemokinin has substance P-like function and expression in inflammation.
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.
Metwali
Ahmed
A
Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Iowa, Iowa City, IA 52242, USA.
Blum
Arthur M
AM
Elliott
David E
DE
Setiawan
Tommy
T
Weinstock
Joel V
JV
D000818:Animals; D002460:Cell Line; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000502:physiology*; D015320:Tachykinins / Q000235:genetics / Q000502:physiology*
D011498:Protein Precursors; D018040:Receptors, Neurokinin-1; C423233:Tac4 protein, mouse; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D007371:Interferon-gamma