Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Suppression of IFN-g Production in Murine Splenocytes by Histamine Receptor Antagonists

Version 1 : Received: 19 November 2018 / Approved: 20 November 2018 / Online: 20 November 2018 (05:35:39 CET)

A peer-reviewed article of this Preprint also exists.

Kamei, M.; Otani, Y.; Hayashi, H.; Nakamura, T.; Yanai, K.; Furuta, K.; Tanaka, S. Suppression of IFN-γ Production in Murine Splenocytes by Histamine Receptor Antagonists. Int. J. Mol. Sci. 2018, 19, 4083. Kamei, M.; Otani, Y.; Hayashi, H.; Nakamura, T.; Yanai, K.; Furuta, K.; Tanaka, S. Suppression of IFN-γ Production in Murine Splenocytes by Histamine Receptor Antagonists. Int. J. Mol. Sci. 2018, 19, 4083.

Abstract

Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues should modulate tumor immunity. We found that a transient histamine synthesis was induced in CD11b+Gr-1+splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-γ were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-γ production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-γ production. However, suppression of IFN-γ production by these antagonists was also found when splenocytes were derived from the Hdc-/- BALB/c mice. Suppressive effects of these antagonists were found on IFN-γ production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H1 and H2 receptors, but not H3 and H4 receptors. IFN-γ production in the Hh1r-/- splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide could suppress IFN-γ production in activated splenocytes in histamine-independent manner.

Keywords

IFN-γ; histamine; splenocyte; histamine H1 receptor, histidine decarboxylase

Subject

Biology and Life Sciences, Immunology and Microbiology

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