Preprint Article Version 1 This version is not peer-reviewed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.

Journal reference: Int. J. Mol. Sci. 2018, 19, 4083
DOI: 10.3390/ijms19124083

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.

Subject Areas

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

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