Immune-mediated β-cell destruction in vitro and in vivo—A pivotal role for galectin-3

Karlsen, Allan E.; Størling, Zenia M.; Sparre, Thomas; Larsen, Martin R.; Mahmood, Amer; Størling, Joachim; Roepstorff, Peter; Wrzesinski, Krzysztof; Larsen, Peter Mose; Fey, Stephen J.; Nielsen, Kristina Tomra; Heding, Peter E.; Ricordi, Camillo; Johannesen, Jesper; Kristiansen, Ole Peter; Bjerre-Christensen, Ulla; Kockum, Ingrid; Luthman, Holger; Nerup, Jørn; Pociot, Flemming

doi:10.1016/j.bbrc.2006.03.105

Cited by 38 publications

(42 citation statements)

References 53 publications

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“…34 In contrast, proteome analysis of isolated Langerhans rat islets exposed to IL-1b identified gal-3 as the most upregulated protein. 35 Upregulation of gal-3 mRNA expression in human islets treated with IL-1b, TNF-a, IFN-g or a mix of these cytokines was also reported. 35 We report that knocking down gal-3 in DLD-1 cells results in a sensitization to CM-LAM, as evidenced by MTT assays and PARP cleavage.…”

Section: Discussionmentioning

confidence: 99%

“…35 Upregulation of gal-3 mRNA expression in human islets treated with IL-1b, TNF-a, IFN-g or a mix of these cytokines was also reported. 35 We report that knocking down gal-3 in DLD-1 cells results in a sensitization to CM-LAM, as evidenced by MTT assays and PARP cleavage. This is in accordance with different articles describing the antiapoptotic activity of gal-3, in response to a wide range of apoptotic insults such as staurosporine, anti-fas antibodies, nitric oxide, radiation, anoikis and TNF-a.…”

Section: Discussionmentioning

confidence: 99%

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Expression of galectin-3 in the tumor immune response in colon cancer

Dumont

Berton

Nagy

et al. 2008

Laboratory Investigation

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The role of tumor-associated macrophages (TAMs) is controversial. Although most studies on different cancer types associate them with a poorer prognosis, interestingly in colon cancer, most articles indicate that TAMs prevent tumor development; patients with high TAMs have better prognosis and survival rate. M1-polarized macrophages produce high level of tumor necrosis factor-a, interleukin-1b or reactive oxygen species, which can effectively kill susceptible tumor cells. In contrast, M2-polarized macrophages can secrete different factors that promote tumor cell growth and survival or favor angiogenesis and tissue invasion. Considering the beneficial role of TAMs in colon cancer, we speculated that they may not display the M2 polarization commonly observed in tumor microenvironment, but rather develop M1 properties. Therefore, we used an in vitro model to analyze the effects of supernatants from M1-polarized macrophages on DLD-1 colon cancer cells. Our data indicate that the conditioned medium from LPS-activated macrophages (CM-LAM) contains a high level of granulocyte-macrophage colony-stimulating factor, interleukins-1b, -6, -8 and tumor necrosis factor-a, and that it exerts a marked growth inhibitory activity on DLD-1 cells. Prolonged exposure to CM-LAM results in cell death by apoptosis. Such exposure to CM-LAM leads to the modulation of gal-3 expression: we observed a marked downregulation of gal-3 mRNA and protein expression following CM-LAM treatment. We also describe that the knockdown of gal-3 sensitizes DLD-1 cells to CM-LAM. These data suggest an involvement of gal-3 in the response of colon cancer cells to proinflammatory stimuli, such as the conditioned medium from activated macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression of galectin-3 in the tumor immune response in colon cancer

Dumont

Berton

Nagy

et al. 2008

Laboratory Investigation

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“…110 Gal-3 protects pancreatic b cells against IL-1-mediated apoptosis. 111 On the other hand, inhibition or deletion of galectin-3 renders pancreatic b-cells more resistant to TNF-a/IFN-g/IL-1b apoptosis. 112 Probably, extracellular and intracellular gal-3 have a different effect in T1D pathogenesis.…”

Section: Type I Diabetes (T1d)mentioning

confidence: 99%

Galectin-3 in autoimmunity and autoimmune diseases

Oliveira

Gatto

Bassi

et al. 2015

Exp Biol Med (Maywood)

143

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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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“…[19,20] Thus, the goal of determining the effect of this biomarker on the progression of dysglycemia and cardiovascular remodeling in patients with AH and comorbid type 2 DM is attracting considerable interest in clinical practice.…”

Section: [18]mentioning

confidence: 99%

Galectin-3 as a potential biomarker of metabolic disorders and cardiovascular remodeling in patients with hypertension and type 2 diabetes

Bobronnikova¹

2017

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How to cite this article: Bobronnikova L. Galectin-3 as a potential biomarker of metabolic disorders and cardiovascular remodeling in patients with hypertension and type 2 diabetes. Vessel Plus 2017;1:61-7. Aim:To determine the impact of galectin-3 levels on the progression of metabolic disorders and structural-functional changes in the myocardium and blood vessels in patients with concomitant systemic arterial hypertension (AH) and type 2 diabetes mellitus (type 2 DM). Methods: Ninety-five patients with hypertension stage II grade 2 (53 males and 42 females) were examined. The patients were separated: group 1 (n = 32) patients with AH, without carbohydrate metabolism disorders; group 2 (n = 30) patients with AH and pre-diabetes; group 3 (n = 33) concomitant AH and type 2 DM. Carbohydrate metabolism, insulin resistance parameters and galectin-3 levels were measured. Echocardiography was performed to determine the structural-functional condition of the heart. Estimation of the intima-media complex thickness of the common carotid artery was performed by duplex ultrasound scanning. Results: Hypertrophy of the left ventricular myocardium is most evident in patients with AH and type 2 DM compared with groups 1 and 2, and the control group (P < 0.05). The levels of galectin-3 in the group with concomitant hypertension and type 2 DM were higher than in groups 1 and 2, and the control group (P < 0.05). A positive correlation was revealed between the level of galectin-3, indices of insulin resistance, and structural-functional cardiac and vessel remodeling. Conclusion: Galectin-3 levels in serum are significantly linked with indices of insulin resistance and cardiovascular remodeling. Key words:Arterial hypertension, type 2 diabetes mellitus, insulin resistance, cardiovascular remodeling, galectin-3 ABSTRACTArticle history:

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Immune-mediated β-cell destruction in vitro and in vivo—A pivotal role for galectin-3

Cited by 38 publications

References 53 publications

Expression of galectin-3 in the tumor immune response in colon cancer

Expression of galectin-3 in the tumor immune response in colon cancer

Galectin-3 in autoimmunity and autoimmune diseases

Galectin-3 as a potential biomarker of metabolic disorders and cardiovascular remodeling in patients with hypertension and type 2 diabetes

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