Search Results (3)

Background: Osteoarthritis (OA) is a chronic degenerative whole joint disease characterized by cartilage breakdown and inflammation. Galectin-3 (Gal-3), a β-galactoside-binding lectin secreted into the extracellular space, binds to glycosylated components of the extracellular matrix (ECM), modulating cell–matrix interactions and inflammation. This study aims to evaluate the anti-inflammatory effects of Hylach^®, a hyaluronic acid (HA) derivative conjugated with lactose-based residues that bind Gal-3, on in vitro inflamed primary human chondrocytes. Methods: Chondrocyte viability, after both Hylach^® and HA treatments at different concentrations was assessed using the MTT assay. Two-dimensional and 3D cell cultures exposed to the conditioned medium (CM) of activated U937 monocytes and subsequently treated with Hylach or HA, were analyzed for the expression of IL-1β, IL-6, TNF-α, and Gal-3 at different time points (4, 10, and 24 h). Results: HA and Hylach^® did not affect cell viability at any of the tested concentrations. Both molecules reduced the overexpression of Gal-3 and pro-inflammatory molecules in 2D inflamed cell cultures, at both gene and protein levels. Notably, IL-1β, IL-6 and Gal-3 showed a more pronounced inhibitory effect at 4 h, with Hylach demonstrating a stronger reduction compared to native HA. Moreover, in inflamed 3D chondrocyte cultures, Hylach^® but not HA, significantly reduced IL-1β, TNF-α and Gal-3 gene expression. Conclusions: Hylach^® exerts an early and more potent anti-inflammatory effect in inflamed 2D and 3D chondrocyte cultures when compared to HA. These findings suggest that targeting Gal-3 through selective HA derivatives may represent a promising strategy for modulating both inflammation and matrix remodelling in OA. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory and fibrotic pathological condition with undefined effective therapies and a poor prognosis, partly due to the lack of specific and effective therapies. Galectin 3 (Gal-3), a pro-fibrotic ß-galactoside binding lectin, was upregulated in the early stages of the pathology, suggesting that it may be considered a marker of active fibrosis. In the present in vitro study, we use Hylach^®, a lactose-modified hyaluronic acid able to bind Gal-3, to prevent the activation of lung myofibroblast and the consequent excessive ECM protein cell expression. Primary human pulmonary fibroblasts obtained from normal and IPF subjects activated with TGF-β were used, and changes in cell viability, fibrotic components, and pro-inflammatory mediator expression at both gene and protein levels were analyzed. Hylach compounds with a lactosylation degree of about 10% and 30% (Hylach1 and Hylach 2), administrated to TGF-β—stimulated lung fibroblast cultures, significantly downregulated α-smooth muscle actin (α-SMA) gene expression and decreased collagen type I, collagen type III, elastin, fibronectin gene and protein expression to near baseline values. This anti-fibrotic activity is accompanied by a strong anti-inflammatory effect and by a downregulation of the gene expression of Smad2 for both Hylachs in comparison to the native HA. In conclusion, the Gal-3 binding molecules Hylachs attenuated inflammation and TGF-β—induced over-expression of α-SMA and ECM protein expression by primary human lung fibroblasts, providing a new direction for the treatment of pulmonary fibrotic diseases. Full article

The progression of smoking-related diseases is characterized by macrophage-mediated inflammation, which is responsible for an increased expression of proinflammatory cytokines and galectins, molecules that bind specifically to β-galactoside sugars. This study aimed to assess the anti-inflammatory and antioxidant effects of a broad selection of differently lactose-modified hyaluronic acids (HA) named HYLACH^®, which are able to bind proinflammatory galectins. The best HYLACH ligands for Gal-3 were selected in silico and their activities were tested in vitro on primary human bronchial fibroblasts obtained from smokers and inflamed with the conditioned medium of activated U937 monocytes. Changes in cell viability, ROS generation, proinflammatory mediators, and MMP expression, at both gene and protein levels, were analyzed. The in silico results show that HYLACH with a percentage of lactosylation of 10–40% are the best ligands for Gal-3. The in vitro study revealed that HYLACH compounds with 10, 20, and 40% lactosylation (HYLACH-1-2-3) administrated to inflamed cell cultures counteracted the oxidative damage and restored gene and protein expression for IL-1β, TNF-α, IL-6, Gal-1, Gal-3, and MMP-3 to near baseline values. The evidence that HYLACH attenuated macrophage-induced inflammation, inhibited MMP expression, and exhibited antioxidative effects provide an initial step toward the development of a therapeutic treatment suitable for smoking-related diseases. Full article