Nitric oxide mediates T cell cytokine production and signal transduction in histidine decarboxylase knockout mice

A. Koncz, Maria Pasztoi, Mercedesz Mazan, Ferenc Fazakas, E. Búzás, A. Falus, Gyorgy Nagy

Research output: Contribution to journalArticle

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Abstract

Histamine is a key regulator of the immune system. Several lines of evidence suggest the role of histamine in T cell activation and accelerated Th1 immune response is a hallmark of histidine decarboxylase knockout (HDC-KO) mice, with a complete lack of endogenously produced histamine. According to our previous work, T lymphocytes produce NO upon activation, and NO is necessary for effective T cell activation. To study the role of histamine in T cell activation, we investigated cytokine production and T cell signal transduction in HDC-KO and wild-type (WT) mice. In the absence of histamine, an elevated IFN-γ mRNA and protein levels of splenocytes (p <0.001; p = 0.001, respectively) were associated with a markedly increased (2.5-fold, p = 0.0009) NO production, compared with WT animals. Furthermore, histamine treatment decreased the NO production of splenocytes from both WT and HDC-KO mice (p = 0.001; p = 0.0004, respectively). NO precursor (Z)-1-[2-(2-aminoethyl)-N-(2- ammonioethyl) amino] diazen-1-ium-1,2-diolate-diethylenetriamine elicited IFN-γ production (p = 0.0002), whereas NO synthase inhibitors N G-monomethyl-L-arginine and nitronidazole both inhibited IFN-γ production (p = 0.002 and p = 0.01, respectively), suggesting the role of NO in regulating IFN-γ synthesis. Cytoplasmic Ca2+ concentration of unstimulated T cells was increased in the HDC-KO mice (p = 0.02), whereas T cell activation-induced δ Ca2+-signal was similar in both HDC-KO and WT animals. Our present data indicate that, in addition to its direct effects on T lymphocyte function, histamine regulates cytokine production and T cell signal transduction through regulating NO production.

Original languageEnglish
Pages (from-to)6613-6619
Number of pages7
JournalJournal of Immunology
Volume179
Issue number10
Publication statusPublished - Nov 15 2007

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Histidine Decarboxylase
Knockout Mice
Signal Transduction
Nitric Oxide
Histamine
Cytokines
T-Lymphocytes
Wild Animals
Nitric Oxide Synthase
Arginine
Immune System

ASJC Scopus subject areas

  • Immunology

Cite this

Nitric oxide mediates T cell cytokine production and signal transduction in histidine decarboxylase knockout mice. / Koncz, A.; Pasztoi, Maria; Mazan, Mercedesz; Fazakas, Ferenc; Búzás, E.; Falus, A.; Nagy, Gyorgy.

In: Journal of Immunology, Vol. 179, No. 10, 15.11.2007, p. 6613-6619.

Research output: Contribution to journalArticle

Koncz, A. ; Pasztoi, Maria ; Mazan, Mercedesz ; Fazakas, Ferenc ; Búzás, E. ; Falus, A. ; Nagy, Gyorgy. / Nitric oxide mediates T cell cytokine production and signal transduction in histidine decarboxylase knockout mice. In: Journal of Immunology. 2007 ; Vol. 179, No. 10. pp. 6613-6619.
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