Galectin-9 enhances cytokine secretion, but suppresses survival and degranulation, in human mast cell line

半乳糖凝集素-9 增强细胞因子分泌,但抑制人类肥大细胞系的存活和脱颗粒

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作者:Reiji Kojima, Tatsukuni Ohno, Motoyasu Iikura, Toshiro Niki, Mitsuomi Hirashima, Keichi Iwaya, Hitoshi Tsuda, Shigeaki Nonoyama, Akio Matsuda, Hirohisa Saito, Kenji Matsumoto, Susumu Nakae

Abstract

Galectin-9 (Gal-9), a lectin having a β-galactoside-binding domain, can induce apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FcεRI. Gal-9 induced apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells.

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