Biomaterial Database

Interleukin-4, an inhibitor of cartilage breakdown in bovine articular cartilage explants. 1995

L A Yeh, and A J Augustine, and P Lee, and L R Riviere, and A Sheldon

Department of Enzyme Biochemistry, OsteoArthritis Sciences, Inc., Cambridge, MA 02139, USA.

OBJECTIVE To determine the ability of interleukin-4 (IL-4) to inhibit the degradation of proteoglycan in bovine articular cartilage explants stimulated by human interleukin-1 (IL-1 alpha), tumor necrosis factor (TNF-alpha), a combination of TNF-alpha and IL-1 alpha, and lipopolysaccharide (LPS). METHODS 35SO4 radiolabelled bovine radiocarpal cartilage explants were treated with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS, plus various concentrations of IL-4 for 72 h. Proteoglycan released to the media was analyzed by scintillation counting and composite gel electrophoresis. Media samples were also analyzed by Western immunoblotting for metalloproteinases and TIMP. RESULTS IL-4 significantly reduced the cartilage proteoglycan degradation induced by IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS (50% inhibitory concentration, IC50 for IL-4 ranged from about 15 to 50 ng/ml). Western blotting showed that media stromelysin levels were increased by IL-1 alpha, TNF-alpha, and LPS, but that IL-4 had no observable effect. Composite gel electrophoresis demonstrated quantitative and qualitative differences in proteoglycan degradation after IL-4 treatment. CONCLUSIONS IL-4 has a potent inhibitory effect on cartilage degradation after stimulation with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS. These results suggest that IL-4 should be investigated further for therapeutic value as a chondroprotective agent for the treatment of arthritis.

UI	MeSH Term	Description	Entries
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D011509	Proteoglycans	Glycoproteins which have a very high polysaccharide content.	Proteoglycan,Proteoglycan Type H
D002358	Cartilage, Articular	A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.	Articular Cartilage,Articular Cartilages,Cartilages, Articular
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D015847	Interleukin-4	A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.	B-Cell Growth Factor-I,B-Cell Stimulatory Factor-1,Binetrakin,IL-4,Mast Cell Growth Factor-2,B Cell Stimulatory Factor-1,B-Cell Growth Factor-1,B-Cell Proliferating Factor,B-Cell Stimulating Factor-1,B-Cell Stimulatory Factor 1,BCGF-1,BSF-1,IL4,MCGF-2,B Cell Growth Factor 1,B Cell Growth Factor I,B Cell Proliferating Factor,B Cell Stimulating Factor 1,B Cell Stimulatory Factor 1,Interleukin 4,Mast Cell Growth Factor 2