Anti-inflammatory Property of Galectin-1 in a Murine Model of Allergic Airway Inflammation

Abstract

Galectin-1 (Gal-1) has immunomodulatory activities in various allergic inflammatory disorders, but its potential anti-inflammatory properties on allergic airway diseases have not been confirmed. We explored the pharmacological effects of Gal-1 on the progression of allergic airway inflammation and investigated the underlying mechanism. Female C57BL/6 mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-17 to establish an allergic airway inflammation model. In the challenge phase, a subset of mice was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). We found that rGal-1 inhibited pulmonary inflammatory cell recruitment, mucus secretion, bronchoalveolar lavage fluid (BALF) inflammatory cell infiltration, and cytokine production. The treatment also suppressed the infiltration of eosinophils into the allergic lung as indicated by decreased expression levels of eotaxin and eosinophil peroxidase (EPX). However, only the expression levels of IL-25, neither IL-33 nor TSLP, were significantly decreased in the lung by rGal-1 treatment. These immunomodulatory effects in the allergic lung were correlated with the activation of extracellular signal-regulated kinase (ERK) signaling pathway and downregulation of endogenous Gal-1. In addition, rGal-1 reduced the plasma concentrations of anti-OVA immunoglobulin E (IgE) and IL-17. Our findings suggest that rGal-1 is an effective therapy for allergic airway inflammation in a murine model and may be a potential pharmacological target for allergic airway inflammatory diseases.

Galectin-1 Expression in CD8+ T Lymphocytes Controls Inflammation in Contact Hypersensitivity

“…Pharmacological interventions with recombinant Gal-1 protein plays an essential immunoregulatory role by inhibiting CD4 + T-cell effector functions in different pathologies J o u r n a l P r e -p r o o f such as Crohn's disease (Santucci et al, 2003), multiple sclerosis (Toscano et al, 2007) or asthma (Lv et al, 2019). Previous studies have shown that the interaction between Gal-1 and CD69 modulates Th17 effector cell differentiation and function (de la Fuente et al, 2014).…”

Galectins in Cancer and the Microenvironment: Functional Roles, Therapeutic Developments, and Perspectives

“…To date, these Gals have been found to regulate different cellular functions, including the interaction of galactoside ligands with different proteins in embryonic development, inflammation, immune response, metabolic disease, premRNA splicing, cell cycle, motility, survival, organ fibrosis, and cancer development (Figure 2) [9][10][11][12][13][14][15]. Gals are involved in cell proliferation, migration, anti-apoptosis, carbohydrates, proteins, lipid metabolism or nucleic acid synthesis, resistance to drug treatment, immune system or inflammation response, vessel generation, organ fibrogenesis, and resistance to death.…”

“…To date, these Gals have been found to regulate different cellular functions, including the interaction of galactoside ligands with different proteins in embryonic development, inflammation, immune response, metabolic disease, premRNA splicing, cell cycle, motility, survival, organ fibrosis, and cancer development ( Figure 2 ) [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…Inflammatory bowel disease patients produce high serum levels of Gal-1 and Gal-3 [ 24 ]. Moreover, recombinant Gal-1 attenuates anti-ovalbumin glucose immunoglobulin E and interleukin to alleviate allergic airway inflammation [ 12 ]. Recombinant Gal-9 reverses lipopolysaccharide (LPS)-induced preeclampsia by promoting M2 macrophage polarization [ 25 ].…”

The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation

“…In order to evaluate Gal 1 as a potential therapeutic protein, Ly et al have shown that the recombinant Gal 1 protects from allergic asthma in a mouse model (22). The immunomodulatory effects in the allergic lung were correlated with the activation of the extracellular signal-regulated kinase signaling pathway and downregulation of endogenous Gal-1.…”