Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1β-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-κB and p38

Abstract

HA suppresses IL-1beta-enhanced MMP-1 and MMP-3 synthesis in RSF via ICAM-1 through down-regulation of NF-kappaB and p38. Intra-articular injection of HA of high molecular weight may work through such a mechanism in RA joints.

Hyaluronan Inhibits Prostaglandin E2 Production via CD44 in U937 Human Macrophages

“…This study extended our previous findings (Yasuda 2007) and has shown that HA inhibits PGE 2 production by COX-2 suppression through down-regulation of NF-κ B in LPS-activated U937 cells. Inhibitory effect of HA on PGE 2 production in IL-1-stimulated RA synovial fibroblasts (Tamoto et al 1994) could be caused through a similar mechanism because HA can down-regulate NF-κ B activation by IL-1 in the cells (Hiramitsu et al 2006). Furthermore, clinical improvement of RA knee pain after intra-articular injection of HA (Matsuno et al 1999) may result from a decrease in PGE 2 by synovial macrophages and fibroblasts through NF-κ B suppression by HA.…”

“…HA suppresses proinflammatory cytokine-stimulated production of matrix metalloproteinases (MMPs) via CD44 (Shimizu et al 2003) and ICAM-1 (Hiramitsu et al 2006) in RA synovial fibroblasts and via CD44 in OA articular chondrocytes (Julovi et al 2004). Whereas proinflammatory cytokines activate some specific intracellular signaling pathways including mitogenactivated protein kinases (MAPKs) and nuclear factor (NF)-κ B, the receptor-HA binding could result in alteration in such signaling cascades because HA inhibits interleukin (IL)-1β -induced activation of p38 MAPK and NF-κ B via ICAM-1 (Hiramitsu et al 2006). In addition to MMPs, HA can suppress PGE 2 production in IL-1α -stimulated OA (Yasui et al 1992) and RA (Tamoto et al 1994) synovial fibroblasts.…”

Comparison of hyaluronan effects among normal, osteoarthritis, and rheumatoid arthritis cartilages stimulated with fibronectin fragment

“…As shown in our previous studies in RA synovial fibroblasts (42), HBFN-f may act through this integrin in OA and RA chondrocytes. While HA can inhibit non-CD44-binding cytokines via HA receptor through suppression of p38 and NF-κB (7,13), HA suppresses HBFN-f action through NF-κB downregulation (39). This indicates additional inhibitory mechanism that HA interaction with highly expressed CD44 in OA and RA cartilages activates some intracellular pathways that suppress catabolic events by HBFN-f via α4β1 integrin or other receptor(s), which is under investigation.…”

“…HA associates with several cell surface proteins such as CD44 (3) and intercellular adhesion molecule-1 (ICAM-1) (7), which are constitutively expressed in chondrocytes (5,14). There is an increasing body of evidence that HA action is mediated through its receptors (7,13,14,36). Exogenous FN-fs can penetrate articular cartilage and accumulate around chondrocytes (15).…”

Activated Protein C Inhibits Proliferation and Tumor Necrosis Factor α-Stimulated Activation of p38, c-Jun NH2-Terminal Kinase (JNK) and Akt in Rheumatoid Synovial Fibroblasts

“…RSFs, human dermal fibroblasts (HDFs) and mouse dermal fibroblasts (MDFs) were obtained from RA synovium, dermis of neonatal foreskin and C57BL/6J mouse skin, respectively, by enzymatic digestions as described previously (25). Briefly, tissues were minced into small pieces and digested with 2 mg/mL collagenase (Sigma-Aldrich, St. Louis, MO, USA) in Dulbecco's modified Eagle medium (DMEM) containing 100 U/mL penicillin, 100 μg/mL streptomycin, 10 mmol/L HEPES (all from Gibco BRL/Life Technologies, Carlsbad, CA, USA) and 3.7 g/L NaHCO 3 at 37°C for 3 h, followed by digestion with 0.25% trypsin and 0.02% ethylenediaminetetraacetic acid (EDTA) at 37°C for 30 min.…”