IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation

Razvan Arsenescu, Arthur M. Blum, Ahmed Metwali, David E. Elliott, Joel V. Weinstock

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Substance P (SP), a neuropeptide, interacts with the neurokinin 1 receptor (NK-1R) on immune cells to help control IFN-γ production. In marine schistosomiasis mansoni, schistosome worms produce ova that incite focal Th2-type granulomatous inflammation within the liver and intestines. Normal gut is characterized by a controlled state of inflammation. IL-10 knockout mice develop chronic Th1-type colitis spontaneously. Both schistosome granulomas and gut mucosa display an SP immune regulatory circuit. However, the origin and regulation of SP production at these sites of inflammation are poorly understood. Macrophages are a potential source of SP. We therefore studied macrophages (F4/80 + ) from these models of inflammation. SP mRNA (pre-protachykinin A (PPT A)) was detected within the schistosome granuloma, spleen, and lamina propria macrophages. Compared with those from wild-type mice, granuloma macrophages from STAT6 -/- mice had 10-fold higher PPT A mRNA expression, whereas in STAT4 -/- animals, PPT A mRNA expression was nearly abolished. IL-12 signals via STAT4 to induce Th1-type inflammation. It was demonstrated that EL-12, but not IL-18, induces SP mRNA expression in resting splenic macrophages from Schistosoma-infected mice and in wild-type lamina propria mononuclear cells. Thus, macrophages are a source for SP at these sites of chronic inflammation, and IL-12 and STAT4 are regulators of macrophage SP mRNA expression.

Original languageEnglish (US)
Pages (from-to)3906-3911
Number of pages6
JournalJournal of Immunology
Volume174
Issue number7
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Fingerprint

Interleukin-12
Substance P
Spleen
Macrophages
Inflammation
Messenger RNA
Granuloma
Mucous Membrane
Schistosoma
Neurokinin-1 Receptors
Schistosomiasis mansoni
Interleukin-18
Colitis
Neuropeptides
Knockout Mice
Interleukin-10
Intestines
Ovum
Liver
protachykinin

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Arsenescu, Razvan ; Blum, Arthur M. ; Metwali, Ahmed ; Elliott, David E. ; Weinstock, Joel V. / IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation. In: Journal of Immunology. 2005 ; Vol. 174, No. 7. pp. 3906-3911.
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IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation. / Arsenescu, Razvan; Blum, Arthur M.; Metwali, Ahmed; Elliott, David E.; Weinstock, Joel V.

In: Journal of Immunology, Vol. 174, No. 7, 01.04.2005, p. 3906-3911.

Research output: Contribution to journalArticle

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