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Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-kappaB and p38.
Rheumatology (Oxford). 2006 Jul; 45(7):824-32.R

Abstract

OBJECTIVE

In rheumatoid arthritis (RA), it is well known that rheumatoid synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown that hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates HA effects only partially, and intracellular events after the HA binding to its receptors remain unclear. We investigated the role of intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA, and the intracellular signalling pathways in the actions of HA.

METHODS

RSF were isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta in the presence of HA, or IL-1beta in the presence of HA with pretreatment with anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by immunoblotting.

RESULTS

Production of MMP-1 and MMP-3 by RSF was stimulated by IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1 antibody at 50 mug/ml significantly blocked the effects of HA on the actions of IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry. Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation of NF-kappaB and p38 without affecting JNK.

CONCLUSION

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.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo, Kyoto 606-8507, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16449361

Citation

Hiramitsu, T, et al. "Intercellular Adhesion Molecule-1 Mediates the Inhibitory Effects of Hyaluronan On Interleukin-1beta-induced Matrix Metalloproteinase Production in Rheumatoid Synovial Fibroblasts Via Down-regulation of NF-kappaB and P38." Rheumatology (Oxford, England), vol. 45, no. 7, 2006, pp. 824-32.
Hiramitsu T, Yasuda T, Ito H, et al. Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-kappaB and p38. Rheumatology (Oxford). 2006;45(7):824-32.
Hiramitsu, T., Yasuda, T., Ito, H., Shimizu, M., Julovi, S. M., Kakinuma, T., Akiyoshi, M., Yoshida, M., & Nakamura, T. (2006). Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-kappaB and p38. Rheumatology (Oxford, England), 45(7), 824-32.
Hiramitsu T, et al. Intercellular Adhesion Molecule-1 Mediates the Inhibitory Effects of Hyaluronan On Interleukin-1beta-induced Matrix Metalloproteinase Production in Rheumatoid Synovial Fibroblasts Via Down-regulation of NF-kappaB and P38. Rheumatology (Oxford). 2006;45(7):824-32. PubMed PMID: 16449361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-kappaB and p38. AU - Hiramitsu,T, AU - Yasuda,T, AU - Ito,H, AU - Shimizu,M, AU - Julovi,S M, AU - Kakinuma,T, AU - Akiyoshi,M, AU - Yoshida,M, AU - Nakamura,T, Y1 - 2006/01/31/ PY - 2006/2/2/pubmed PY - 2006/8/17/medline PY - 2006/2/2/entrez SP - 824 EP - 32 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 45 IS - 7 N2 - OBJECTIVE: In rheumatoid arthritis (RA), it is well known that rheumatoid synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown that hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates HA effects only partially, and intracellular events after the HA binding to its receptors remain unclear. We investigated the role of intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA, and the intracellular signalling pathways in the actions of HA. METHODS: RSF were isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta in the presence of HA, or IL-1beta in the presence of HA with pretreatment with anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by immunoblotting. RESULTS: Production of MMP-1 and MMP-3 by RSF was stimulated by IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1 antibody at 50 mug/ml significantly blocked the effects of HA on the actions of IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry. Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation of NF-kappaB and p38 without affecting JNK. CONCLUSION: 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. SN - 1462-0324 UR - https://www.unboundmedicine.com/medline/citation/16449361/Intercellular_adhesion_molecule_1_mediates_the_inhibitory_effects_of_hyaluronan_on_interleukin_1beta_induced_matrix_metalloproteinase_production_in_rheumatoid_synovial_fibroblasts_via_down_regulation_of_NF_kappaB_and_p38_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kel026 DB - PRIME DP - Unbound Medicine ER -