RESUMO
Evidence is presented for the synthesis of Interleukin-1 (IL-1) by joint synovial tissue and chondrocytes. Purified preparations of mouse and human recombinant forms of this factor stimulate the synthesis of a secretory protease by cartilage. The IL-1 stimulated chondrocyte protease is capable of converting latent collagenase to its active form. Other proteases such as trypsin and the mercurial aminophenyl mercuric acetate will not activate collagenase in the absence of this protease. Evidence is presented showing that chondrocytes synthesize IL-1 suggesting autocrine control of cartilage matrix turnover.
Assuntos
Cartilagem/metabolismo , Interleucina-1/biossíntese , Animais , Bovinos , Ativação Enzimática , Humanos , Técnicas In Vitro , Camundongos , Colagenase Microbiana/metabolismo , Peptídeo Hidrolases/metabolismo , Membrana Sinovial/metabolismoRESUMO
We have purified a low molecular weight protein from medium conditioned by calf synovium with physical and biological properties similar to the leukocyte cytokine interleukin 1 (IL-1). The factor is active in stimulating the synthesis (three- to fivefold) of collagenase activator protein (CAP) by the surface (1-2 mm) of articular cartilage while CAP synthesis in the deeper zones of articular cartilage is not affected. Recombinant mouse IL-1 and commercially available purified human IL-1 are also capable of stimulating cartilage to synthesize and secrete CAP. The synthesis of other proteins, including collagenase, appeared to be unaffected by either the synovial factors or the human and mouse IL-1.
Assuntos
Cartilagem Articular/metabolismo , Interleucina-1/fisiologia , Metaloproteases , Biossíntese de Proteínas , Membrana Sinovial/fisiologia , Animais , Bovinos , Cromatografia/métodos , Meios de Cultura , Eletroforese em Gel de Poliacrilamida , Ativação Enzimática , Técnicas In Vitro , Interleucina-1/isolamento & purificação , Colagenase Microbiana/metabolismoRESUMO
In this report we describe the presence of interleukin-1 activity in medium conditioned by bovine articular cartilage. Preparations partially purified by Sephacryl S200 chromatography (Mr 18000-25000) stimulate murine thymocyte proliferation in the lymphocyte activation factor assay. Furthermore, the factor(s) activate cartilage tissue to secrete a protease which is essential for the activity of purified synovial collagenase. We also demonstrate the presence of mRNA coding for IL-1 alpha and beta in human articular chondrocytes and conclude that the human monocytic and chondrocytic mRNAs are identical. Our results demonstrating cartilage expression of IL-1 genes suggest the possibility of an autocrine mechanism whereby chondrocyte production of matrix degrading proteases is initiated by chondrocyte derived IL-1.