Galectin-3 is a negative regulator of lipopolysaccharide-mediated inflammation.
Galectin-3 is a beta-galactoside-binding lectin that plays an important role in inflammatory diseases. It also interacts with the surface carbohydrates of many pathogens, including LPS. However, its role in infection is not fully understood. Data presented herein demonstrate for the first time that galectin-3 is a negative regulator of LPS-induced inflammation. Galectin-3 is constitutively produced by macrophages and directly binds to LPS. Galectin-3-deficient macrophages had markedly elevated LPS-induced signaling and inflammatory cytokine production compared with wild-type cells, which was specifically inhibited by the addition of recombinant galectin-3 protein. In contrast, blocking galectin-3 binding sites by using a neutralizing Ab or its ligand, beta-lactose, enhanced LPS-induced inflammatory cytokine expression by wild-type macrophages. In vivo, mice lacking galectin-3 were more susceptible to LPS shock associated with excessive induction of inflammatory cytokines and NO production. However, these changes conferred greater resistance to Salmonella infection. Thus, galectin-3 is a previously unrecognized, naturally occurring, negative regulator of LPS function, which protects the host from endotoxin shock but, conversely, favors Salmonella survival.
Li
Yubin
Y
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
Komai-Koma
Mousa
M
Gilchrist
Derek S
DS
Hsu
Daniel K
DK
Liu
Fu-Tong
FT
Springall
Tabitha
T
Xu
Damo
D
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D037502:Galectin 3 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D008050:Lipid A / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012772:Shock, Septic / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
D037502:Galectin 3; D018836:Inflammation Mediators; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4