Chondroitin Sulfate Inhibits Monocyte Chemoattractant Protein-1 Release From 3T3-L1 Adipocytes: A New Treatment Opportunity for Obesity-Related Inflammation?

Thomas V Stabler ； Eulália Montell ； Josep Vergés ； Janet L Huebner ； Virginia Byers Kraus

《Biomarker Insights》 2017卷 (2017/12) Pp. 1-4-015

https://doi.org/10.1177/1177271917726964

摘要

Monocyte chemoattractant protein-1 (MCP-1) overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adipocytes using an established protocol. Adipocytes were treated with lipopolysaccharide (LPS) to induce inflammation and thus MCP-1 release. At the same time, varying concentrations of chondroitin sulfate (CS) were added in a physiologically relevant range (10-200 μg/mL) to determine its impact on MCP-1 release. Chondroitin sulfate, a natural glycosaminoglycan of connective tissue including the cartilage extracellular matrix, was chosen on the basis of our previous studies demonstrating its anti-inflammatory effect on macrophages. Because the main action of MCP-1 is to induce monocyte migration, cultured THP-1 monocytes were used to test whether CS at the highest physiologically relevant concentration could inhibit cell migration induced by human recombinant MCP-1. Chondroitin sulfate (100-200 μg/mL) inhibited MCP-1 release from inflamed adipocytes in a dose-dependent manner (P ＜ .01, 95% confidence interval [CI]: -5.89 to -3.858 at 100 μg/mL and P ＜ .001, 95% CI: -6.028 to -3.996 at 200 μg/mL) but had no effect on MCP-1-driven chemotaxis of THP-1 monocytes. In summary, CS could be expected to reduce macrophage infiltration into adipose tissue by reduction in adipocyte expression and release of MCP-1 and as such might reduce adipose tissue inflammation in response to pro-inflammatory stimuli such as LPS, now increasingly recognized to be relevant in vivo.

關鍵字

Chondroitin sulfate ； adipocytes ； MCP-1 ； chemokines ； LPS