Galectin-9 enhances cytokine secretion, but suppresses survival and degranulation, in human mast cell line.
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.
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.
Reiji
R
Kojima
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Tatsukuni
T
Ohno
Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
Motoyasu
M
Iikura
Departments of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Takamatsu, Japan ; Research Center, GalPharma Company, Takamatsu, Japan.
Toshiro
T
Niki
Departments of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Takamatsu, Japan ; Research Center, GalPharma Company, Takamatsu, Japan.
Mitsuomi
M
Hirashima
Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
Keichi
K
Iwaya
Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
Hitoshi
H
Tsuda
Department of Pediatrics, National Defense Medical College, Saitama, Japan.
Shigeaki
S
Nonoyama
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Akio
A
Matsuda
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Hirohisa
H
Saito
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Kenji
K
Matsumoto
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.
Susumu
S
Nakae
D017209:Apoptosis; D015550:Cell Degranulation; D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation
D016207:Cytokines; D037161:Galectins; C105032:LGALS9 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3