Chondroitin sulphate inhibits NF-κB activity induced by interaction of pathogenic and damage associated molecules

Osteoarthritis Cartilage. 2017 Jan;25(1):166-174. doi: 10.1016/j.joca.2016.08.012. Epub 2016 Sep 7.


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 μg/ml). We measured IL-1β release, intracellular IL-1β, proIL-1β, caspase-1 and NF-κB activity and DNA binding activity of NF-κB transcription factors from nuclear and cytoplasmic extracts.

Results: Serum LPS was significantly associated with radiographic knee joint space narrowing (JSN) (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/ml). 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-1β that were inhibitable by CS. CS did not inhibit caspase-1 activity but in physiologically achievable concentrations, attenuated NF-κB 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-κB transcription factors, p65, p50, c-Rel and RelB.

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-κB transcription factors.

Keywords: Chondroitin sulphate; Hyaluronan; Inflammation; Macrophages; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / pharmacology*
  • Chondroitin Sulfates / pharmacology*
  • Female
  • Humans
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / blood
  • Male
  • Middle Aged
  • NF-kappa B / antagonists & inhibitors*
  • Osteoarthritis, Knee / metabolism
  • THP-1 Cells


  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Chondroitin Sulfates