Induction of interleukin-1 in articular cartilage by explantation and cutting.

Journal article

OBJECTIVE: To investigate the effect of explantation and fine cutting of articular cartilage upon intracellular inflammatory signaling pathways and expression of interleukin-1 (IL-1). METHODS: Cartilage from porcine metacarpophalangeal joints was cultured in serum-free medium. Tissue extracts were examined for ERK activation by phosphorylated-Western blotting, for JNK and p38 MAPK activity by kinase assay, and for IkappaBalpha. IL-1alpha and IL-1beta messenger RNA (mRNA) was measured by reverse transcriptase-polymerase chain reaction. IL-1 activity was measured by the induction of serum amyloid A protein in cultured chondrocytes. RESULTS: All 3 MAPKs (p38, JNK, and ERK) were rapidly activated upon dissection and explantation of the cartilage. IL-1alpha and IL-1beta mRNA was also induced: the speed and magnitude of induction were increased if the explants had been finely cut. IL-1 activity that could be inhibited by IL-1 receptor antagonist or antibodies to IL-1alpha was found in extracts of explants cultured for 20 hours or lysates of cells isolated from them. This activity was likely due to intracellular proIL-1alpha that was not secreted. ProIL-1beta would not be detected because it is biologically inactive. The mechanism of inflammatory signaling pathway activation underlying the induction of IL-1 is unknown. CONCLUSION: Explantation and cutting of articular cartilage activates intracellular inflammatory signaling pathways and induces expression of mRNA for IL-1alpha and IL-1beta. Biologically active IL-1alpha protein was detectable in cartilage lysates and was probably intracellular proIL-1alpha. We were unable to show that IL-1 was secreted by chondrocytes.

Authors: Gruber, J; Vincent, T; Hermansson, M; Bolton, M; Wait, R

• Publication status: Published
• Journal: Arthritis and rheumatism
• Volume: 50
• Issue: 8
• Pages: 2539-2546
• Publication date: 2004-08-01
• DOI: 10.1002/art.20369
• EISSN: 1529-0131
• ISSN: 0004-3591
• Language: English
• Keywords: Culture Techniques; Interleukin-1; RNA, Messenger; Mitogen-Activated Protein Kinase Kinases; Signal Transduction; Chondrocytes; Swine; Cartilage, Articular; MAP Kinase Kinase 4; JNK Mitogen-Activated Protein Kinases; Animals; p38 Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases