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01.04.2009 | Original Article—Alimentary Tract

Cytokine responses of intraepithelial lymphocytes are regulated by histamine H₂ receptor

verfasst von: Kosuke Takagaki, Satoshi Osawa, Yoshiaki Horio, Takanori Yamada, Yasushi Hamaya, Yasuhiro Takayanagi, Takahisa Furuta, Akira Hishida, Mutsuhiro Ikuma

Erschienen in: Journal of Gastroenterology | Ausgabe 4/2009

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Abstract

Backgrounds

Histamine participates in the immune regulation of several gastrointestinal diseases. However, the effect of histamine on intestinal intraepithelial lymphocytes (IELs), the front line of the intestinal mucosal immune system, is not well understood. We examined whether histamine has a direct effect on cytokine production by IELs and the involvement of histamine receptor subtypes.

Methods

Murine IELs were activated by PMA plus ionomycin with/without histamine. Secreted cytokines were measured and compared with those of splenocytes. Intracellular cytokines were detected by flow cytometry. Expression of histamine receptor subtypes in IELs was examined by RT-PCR.

Results

Histamine H₁ receptor (H₁R), H₂R, and H₄R, but not H₃R mRNA were expressed on IELs. Histamine significantly decreased Th1-cytokine (IFN-γ, TNF-α, and IL-2) and also IL-4 production in IELs as well as splenocytes. The selective H₂R antagonist famotidine, but not the H₁R antagonist pyrilamine nor the H₃R/H₄R antagonist thioperamide, competes with the inhibitory effect of histamine on these cytokine production in IELs. These suppressive effects of histamine were mimicked by a selective H₂R/H₄R agonist dimaprit. Further, these suppressive effects of histamine for Th1-cytokine and IL-4 did not accompany the enhancement of IL-10 production or IL-10 mRNA level in IELs. Intracellular cytokine analysis revealed that the number of IFN-γ-producing αβ T cells was significantly reduced by histamine in IELs.

Conclusions

Histamine has a direct suppressive effect on IEL-derived cytokines via H₂R, which would have a crucial role in the suppression of local immunoregulation in the intestinal epithelium.

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Titel: Cytokine responses of intraepithelial lymphocytes are regulated by histamine H2 receptor
verfasst von: Kosuke Takagaki
Satoshi Osawa
Yoshiaki Horio
Takanori Yamada
Yasushi Hamaya
Yasuhiro Takayanagi
Takahisa Furuta
Akira Hishida
Mutsuhiro Ikuma
Publikationsdatum: 01.04.2009
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 4/2009
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-009-0019-9

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Cytokine responses of intraepithelial lymphocytes are regulated by histamine H₂ receptor

Abstract

Backgrounds

Methods

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Conclusions

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Abstract

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