Format

Send to

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

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

Author information

1
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, USA. Electronic address: stablert@hotmail.com.
2
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, USA; Department of Orthopedic Surgery, West China Hospital, West China Medical School, SiChuan University, ChengDu, SiChuan Province, People's Republic of China. Electronic address: Zey.huang@gmail.com.
3
Pre-Clinical R&D Area, Bioibérica, S. A., Barcelona, Spain. Electronic address: lmontell@bioiberica.com.
4
Pre-Clinical R&D Area, Bioibérica, S. A., Barcelona, Spain. Electronic address: jverges@bioiberica.com.
5
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, USA; Division of Rheumatology, Duke University School of Medicine, Durham, USA. Electronic address: kraus004@duke.edu.

Abstract

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

PMID:
27614315
DOI:
10.1016/j.joca.2016.08.012
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center