Abstract
Galectin-3 is a β-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, β-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2781-2789 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 181 |
| Issue number | 4 |
| State | Published - Aug 15 2008 |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
Galectin-3 is a negative regulator of lipopolysaccharide-mediated inflammation. / Li, Yubin; Komai-Koma, Mousa; Gilchrist, Derek S.; Hsu, Daniel K.; Liu, Fu-Tong; Springall, Tabitha; Xu, Damo.
In: Journal of Immunology, Vol. 181, No. 4, 15.08.2008, p. 2781-2789.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Galectin-3 is a negative regulator of lipopolysaccharide-mediated inflammation
AU - Li, Yubin
AU - Komai-Koma, Mousa
AU - Gilchrist, Derek S.
AU - Hsu, Daniel K.
AU - Liu, Fu-Tong
AU - Springall, Tabitha
AU - Xu, Damo
PY - 2008/8/15
Y1 - 2008/8/15
N2 - Galectin-3 is a β-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, β-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.
AB - Galectin-3 is a β-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, β-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.
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M3 - Article
C2 - 18684969
AN - SCOPUS:53149147450
VL - 181
SP - 2781
EP - 2789
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -