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Open AccessArticle

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

1
Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Tsushima naka 1-1-1, Kita-ku, Okayama 700-8530, Japan
2
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University School of Medicine, 1-15-1 Fukumuro, Miyagino-ku, Sendai 983-8536, Japan
3
Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
4
Department of Pharmacology, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho 5, Yamashina-ku, Kyoto 607-8414, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 4083; https://doi.org/10.3390/ijms19124083
Received: 19 November 2018 / Revised: 13 December 2018 / Accepted: 13 December 2018 / Published: 17 December 2018
(This article belongs to the Special Issue Histamine-Related Molecules as Therapeutic Targets)
Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues modulates 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 can suppress IFN-γ production in activated splenocytes in a histamine-independent manner. View Full-Text
Keywords: IFN-γ; histamine; splenocyte; histamine H1 receptor; histidine decarboxylase IFN-γ; histamine; splenocyte; histamine H1 receptor; histidine decarboxylase
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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.

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