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

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

doi:10.1371/journal.pone.0086106

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

PLoS One. 2014 Jan 20;9(1):e86106. doi: 10.1371/journal.pone.0086106. eCollection 2014.

Authors

Affiliations

¹ Department of Basic Pathology, National Defense Medical College, Saitama, Japan ; Department of Pediatrics, National Defense Medical College, Saitama, Japan ; Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
² Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
³ Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
⁴ Departments of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Takamatsu, Japan ; Research Center, GalPharma Company, Takamatsu, Japan.
⁵ Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
⁶ Department of Pediatrics, National Defense Medical College, Saitama, Japan.
⁷ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan ; Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan ; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Cell Degranulation*
Cell Line
Cell Survival
Cytokines / metabolism*
Enzyme Activation
Galectins / metabolism*
Humans
Mast Cells / physiology*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Phosphorylation

Substances

Cytokines
Galectins
LGALS9 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3

Grants and funding

This work was supported by Grants-in-Aid for Young Scientists (B) (T.O.), Scientific Research (C) (M.I.) and Scientific Research (B) (H.S. and K.M.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, by the Program for Improvement of Research Environments for Young Researchers, The Special Coordination Funds for Promoting Science and Technology (S.N.), PRESTO from the Japan Science and Technology Agency, (S.N.), and by Grants-in-Aid from the Japanese Ministry of Health, Labour and Welfare (H.S. and K.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.