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Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process.
J Rheumatol Suppl. 1995 Feb; 43:109-14.JR

Abstract

We investigated the nature of cytokines synthesized by human osteoarthritic (OA) synovium, particularly interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha). We examined the capacity of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) to block the synthesis of metalloproteases (collagenase and stromelysin), IL-1 beta, and IL-6 in osteoarthritis (OA) synovium. Human OA synovium were incubated in the presence or absence of lipopolysaccharide (LPS) or increasing concentrations of rhIL-1ra. The determinations of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-1ra in culture medium were carried out using specific ELISA. Although both IL-1 isoforms and TNF alpha could be produced by OA synovium, IL-1 beta was the predominant cytokine synthesized either in the presence or absence of LPS. Treatment of the OA synovium with an increasing concentration of rhIL-1ra (0-10 micrograms/ml) showed a dose dependent reduction of both metalloproteases and IL-6. Maximal inhibition was 70% for collagenase, 80% for stromelysin, and 76% for IL-6. LPS treated synovium also showed a consistent suppression of metalloproteases and IL-6, although a higher IL-1ra concentration was required. Conversely, IL-1 beta production was not inhibited by IL-1ra, irrespective of the concentration used and whether the membranes were LPS stimulated. These data showed that IL-1 appears to be the major autocrine cytokine involved in the stimulation of metalloproteases and IL-6 synthesis in OA synovium.

Authors+Show Affiliations

Pelletier JP
Louis-Charles Simard Research Center, Notre-Dame Hospital, Department of Medicine, University of Montreal, PQ, Canada.
McCollum R
No affiliation info available
Cloutier JM
No affiliation info available
Martel-Pelletier J
No affiliation info available

MeSH

Culture TechniquesCytokinesEnzyme-Linked Immunosorbent AssayHumansInterleukin 1 Receptor Antagonist ProteinInterleukin-1Interleukin-6LipopolysaccharidesMetalloendopeptidasesOsteoarthritisReceptors, Interleukin-1SialoglycoproteinsSynovial MembraneTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7752112

Clinical Trial Links

Study to Prevent Cartilage Damage Following Acute Knee Injury.

Citation

Pelletier, J P., et al. "Synthesis of Metalloproteases and Interleukin 6 (IL-6) in Human Osteoarthritic Synovial Membrane Is an IL-1 Mediated Process." The Journal of Rheumatology. Supplement, vol. 43, 1995, pp. 109-14.
Pelletier JP, McCollum R, Cloutier JM, et al. Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. J Rheumatol Suppl. 1995;43:109-14.
Pelletier, J. P., McCollum, R., Cloutier, J. M., & Martel-Pelletier, J. (1995). Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. The Journal of Rheumatology. Supplement, 43, 109-14.
Pelletier JP, et al. Synthesis of Metalloproteases and Interleukin 6 (IL-6) in Human Osteoarthritic Synovial Membrane Is an IL-1 Mediated Process. J Rheumatol Suppl. 1995;43:109-14. PubMed PMID: 7752112.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. AU - Pelletier,J P, AU - McCollum,R, AU - Cloutier,J M, AU - Martel-Pelletier,J, PY - 1995/2/1/pubmed PY - 1995/2/1/medline PY - 1995/2/1/entrez SP - 109 EP - 14 JF - The Journal of rheumatology. Supplement JO - J Rheumatol Suppl VL - 43 N2 - We investigated the nature of cytokines synthesized by human osteoarthritic (OA) synovium, particularly interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha). We examined the capacity of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) to block the synthesis of metalloproteases (collagenase and stromelysin), IL-1 beta, and IL-6 in osteoarthritis (OA) synovium. Human OA synovium were incubated in the presence or absence of lipopolysaccharide (LPS) or increasing concentrations of rhIL-1ra. The determinations of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-1ra in culture medium were carried out using specific ELISA. Although both IL-1 isoforms and TNF alpha could be produced by OA synovium, IL-1 beta was the predominant cytokine synthesized either in the presence or absence of LPS. Treatment of the OA synovium with an increasing concentration of rhIL-1ra (0-10 micrograms/ml) showed a dose dependent reduction of both metalloproteases and IL-6. Maximal inhibition was 70% for collagenase, 80% for stromelysin, and 76% for IL-6. LPS treated synovium also showed a consistent suppression of metalloproteases and IL-6, although a higher IL-1ra concentration was required. Conversely, IL-1 beta production was not inhibited by IL-1ra, irrespective of the concentration used and whether the membranes were LPS stimulated. These data showed that IL-1 appears to be the major autocrine cytokine involved in the stimulation of metalloproteases and IL-6 synthesis in OA synovium. SN - 0380-0903 UR - https://www.unboundmedicine.com/medline/citation/7752112/Synthesis_of_metalloproteases_and_interleukin_6__IL_6__in_human_osteoarthritic_synovial_membrane_is_an_IL_1_mediated_process_ L2 - https://ClinicalTrials.gov/search/term=7752112 [PUBMED-IDS] DB - PRIME DP - Unbound Medicine ER -