Galectin 3 aggravates joint inflammation and destruction in antigen‐induced arthritis

Forsman, Huamei; Islander, Ulrika; Andréasson, Emil; Andersson, Annica; Önnheim, Karin; Karlström, Alexandra; Sävman, Karin; Magnusson, Mattias; Brown, Kelly L.; Karlsson, Anna

doi:10.1002/art.30118

Cited by 92 publications

(83 citation statements)

References 44 publications

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“…Joint inflammation and bone erosion associated with methylated BSA-induced arthritis are suppressed in gal3 2/2 mice. Milder disease was accompanied by a reduction in Ag-specific IgG, lower levels of TNF and IL-6, and lower frequency of IL-17A-producing cells (35). These studies showed that the inflammatory response is less severe in mice lacking gal3 and IL-17A, which is pathogenic to EAE, Con Ainduced hepatitis, and Ag-induced arthritis.…”

Section: Discussionmentioning

confidence: 83%

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

Liu

et al. 2013

The Journal of Immunology

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Galectin-3 (gal3) is known for its immunoregulatory functions in infectious, autoimmune, and inflammatory diseases. However, little is known about its regulatory role in the host's IL-17A response to infection. Using a mouse model of histoplasmosis in which both Th1 and Th17 responses contribute to fungal clearance, we investigated how gal3 regulates IL-17A responses. Our study showed that Histoplasma infection induced gal3−/− dendritic cells to produce significantly higher levels of IL-23, TGF-β1, and IL-1β than did gal3+/+ cells. Infected by the same inoculum of Histoplasma, gal3−/− mice had lower fungal burden and produced higher levels of IL-23/IL-17–axis cytokines and lower levels of IL-12 and IFN-γ. Additionally, there was an increase in Th17 cells and a reduction in Th1 cells in infected gal3−/− mice. In vitro Th1/Th17-skewing experiments excluded the intrinsic effect of gal3 on Th cell differentiation. Although neutrophils from both gal3+/+ and gal3−/− mice produced IL-17A upon IL-23 stimulation, their contribution to IL-17A production was greater in gal3−/− mice than in gal3+/+ mice. Compared with gal3+/+ dendritic cells, adoptive transfer of gal3−/− dendritic cells resulted in production of significantly higher levels of IL-17–axis cytokines and reduced fungal burden. It appears that reduced fungal burden and preferential IL-17A response in gal3−/− mice by both Th17 cells and neutrophils were the result of preferential production of IL-23/IL-17–axis cytokines by dendritic cells. Our study showed that gal3 negatively regulates IL-17A responses through inhibition of IL-23/IL-17–axis cytokine production by dendritic cells.

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Section: Discussionmentioning

confidence: 83%

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

Liu

et al. 2013

The Journal of Immunology

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“…It is possible to assume that Galectin-3 could be use as a prognostic circulating biomarker for inflammatory disease, since high levels of Galeetine-3 were found in patients with inflammatory bowel disease (26), arthritis (27) and systemic lupus erythematosus nephritis (28) and its concentrations were positively correlated with C Reactive Protein (29).…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Plasma Levels and Coronary Artery Disease: A New Possible Biomarker of Acute Coronary Syndrome

Falcone

Lucibello

Mazzucchelli

et al. 2011

Int J Immunopathol Pharmacol

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Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27–39.09) vs 6.48 ng/ml (4.88–8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75–29.82) vs 9.18 ng/ml (5.56–23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.

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“…60 Indeed, in RA synovitis, the inflammatory process is orchestrated by activated monocytes (secreting IL-1b, IL-6, IL-7 and tumor necrosis factor-alpha (TNF)-a), fibroblast-like synoviocytes (synthesizing metalloproteases, chemokines and cytokines, mainly IL-15), and dysregulated osteoclasts (due to high levels of TNF-a and IL-17). 61 Gal-3 seems to play a pro-inflammatory role in RA 62 and high serum levels of gal-3 have been found in mice during collagen-induced arthritis. 63 In humans, gal-3 mRNA and protein are overexpressed in the synovial membrane close to joint destruction and are highly correlated with C-reactive protein (CRP) serum levels and IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF), chemokine (C-X-C) motif ligand 8 (CXCL8), metalloproteinase-3 (MMP-3), TNF-a, chemokine (C-C motif) ligand 2 (CCL2), CCL3 and CCL5 secretion by synovial fibroblasts.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

“…64 The lack of gal-3 prevented antigen-induced arthritis in mice which showed lower levels of antigen-specific IgG, IL-6, TNF-a and IL-17. 62 Genetic polymorphisms in gal-3 gene seem to be involved in RA susceptibility. Indeed, it has recently been shown that gal-3 gene (LGALS3) þ 292C allele is associated with RA in Taiwanese population.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Galectin-3 in autoimmunity and autoimmune diseases

Oliveira

Gatto

Bassi

et al. 2015

Exp Biol Med (Maywood)

146

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Galectin-3 (gal-3) is a b-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/ non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra-or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases.

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Galectin 3 aggravates joint inflammation and destruction in antigen‐induced arthritis

Cited by 92 publications

References 44 publications

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

Galectin-3 Plasma Levels and Coronary Artery Disease: A New Possible Biomarker of Acute Coronary Syndrome

Galectin-3 in autoimmunity and autoimmune diseases

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