Galectin-9 protects mice from the Shwartzman reaction by attracting prostaglandin E2-producing polymorphonuclear leukocytes.
Galectins play a crucial role in the modulation of innate and adaptive immunity. Here we show that galectin-9 (Gal-9) exhibits an anti-inflammatory role in LPS-induced inflammation. Intraperitoneal LPS injection enhances Gal-9 levels as well as promotes the production of pro-inflammatory cytokines, e.g., TNF-alpha, IFN-gamma and IL-12. We found that Gal-9 administration results in the protection of mice from the Shwartzman reaction, and Gal-9-deficient mice became susceptible to the Shwartzman reaction, thus implying the anti-inflammatory activity of Gal-9 against LPS-induced inflammation. Indeed, Gal-9 treatment together with LPS suppresses production of these pro-inflammatory cytokines, while it rather enhances than suppresses IL-4 and IL-10 production. We also found that LPS-induced elevation of TNF-alpha, IFN-gamma, and IL-12 does not occur in Gal-9 transgenic mice. Moreover, Gal-9 induces Gr-1(+) cell; probably polymorphonuclear leukocyte (PMN), as well as infiltration in to the peritoneal cavity, causing us to hypothesize PMNs are involved in Gal-9-mediated suppression. The fact that Gal-9 does not suppress LPS-induced TNF-alpha, IFN-gamma and IL-12 production in neutropenic mice, and that it does not protect those mice from the Shwartzman reaction, confirms the involvement of PMN in regulation. PMN attracted by Gal-9 produce PGE(2), which LPS-induced TNF-alpha production from the peritoneal macrophages is suppressed, while PMNs attracted by casein produce less PGE(2) and fail to suppress LPS-induced TNF-alpha production. Our data suggest that Gal-9 regulates LPS-induced inflammation and protects mice from the Shwartzman reaction by attracting PGE(2)-producing PMN.
Tsuboi
Yuka
Y
Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita-gun, Kagawa 761-0793, Japan.
Abe
Hiroko
H
Nakagawa
Ryusuke
R
Oomizu
Souichi
S
Watanabe
Kota
K
Nishi
Nozomu
N
Nakamura
Takanori
T
Yamauchi
Akira
A
Hirashima
Mitsuomi
M
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology*; D037161:Galectins / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D018078:Receptors, Prostaglandin E / Q000276:immunology; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012790:Shwartzman Phenomenon / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D037161:Galectins; D008070:Lipopolysaccharides; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C508186:galectin 9, mouse; D016753:Interleukin-10; D015232:Dinoprostone