Objective: To evaluate the anti-inflammatory mechanism of action of Chondroitin Sulphate (CS).
Design: THP-1 macrophages were cultured with a range of sizes and concentrations of HA fragments with TLR4 (LPS in a physiologically relevant concentration determined by analyses of sera of a community clinic ascertained knee osteoarthritis (OA) cohort) or TLR2 (heat killed listeria bacteria) agonists and varying concentrations of CS in a physiologically relevant range (10-200 mu g/ml). We measured IL-1 beta release, intracellular IL-1 beta ,proIL-1 beta, caspase-1 and NF-kappa B activity and DNA binding activity of NF-kappa B transcription factors from nuclear and cytoplasmic extracts.
Results: Serum LPS was significantly associated with radiographic knee joint space narrowing USN) (P = 0.02) in the OA cohort (n = 40). The priming dose of LPS used for these experiments (10 ng/ml) was below the lowest serum concentration of the OA cohort (median 47.09, range 14.43-81.36 ng/m1). Priming doses of LPS and HA fragments alone did not elicit an inflammatory response. However, primed with LPS, HA fragments produced large dose-dependent increases in IL-1 beta that were inhibitable by CS. CS did not inhibit caspase-1 activity but in physiologically achievable concentrations, attenuated NF-kappa B activity induced by either the TLR4 (LPS 1000 ng/ml) or TLR2 agonists alone or in combination with HA fragments. LPS induced and CS significantly reduced activity of canonical NF-kappa B transcription factors, p65, p50, c-Rel and Re1B.
Conclusions: Subinflammatory concentrations of pathogenic (LPS, listeria) and damage associated (HA) molecules interact to induce macrophage-related inflammation. CS works upstream of the inflammasome by inhibiting activation of NF-kappa B transcription factors. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Citation： Stabler T. V., Huang Z., Montell E., Verges J., Kraus V. B.. Chondroitin sulphate inhibits NF-kappa B activity induced by interaction of pathogenic and damage associated molecules. West China medical Virtual Journal, 2000, 1(1): 166-174-. doi: 10.1016/j.joca.2016.08.012 Copy