title: Induction of neutral proteinase and prostanoid production in bovine nasal chondrocytes by interleukin-1 and tumor necrosis factor alpha: modulation of these cellular responses by interleukin-6 and platelet-derived growth factor.
abstract: We have previously reported that recombinant human interleukin-1 (IL-1) stimulates matrix erosion in bovine nasal cartilage explants (R. J. Smith et al., Inflammation 13, 367-382, 1989). This action of IL-1 is believed to be caused by matrix-degrading neutral proteinases produced by activated chrondrocytes. Accordingly, we investigated the effects of recombinant human interleukin-1 alpha (IL-1 alpha), recombinant human interleukin-1 beta (IL-1 beta), and recombinant human tumor necrosis factor alpha (TNF alpha) on bovine nasal chondrocyte (BNC) responsiveness. IL-1 alpha and IL-1 beta stimulated a time (0-72 hr) and concentration-dependent (0.01-10 ng/ml) production of collagenase, gelatinase, caseinase, and prostaglandin E2 (PGE2) in BNC monolayer cultures. Neutral proteinase and PGE2 production by BNC was also induced by TNF alpha (0.2-200 ng/ml) in a time-dependent (0-72 hr) manner. Recombinant human interleukin-6 (IL-6) caused a concentration-dependent (6-200 ng/ml) potentiation of IL-1-stimulated neutral proteinase and PGE2 production by BNC. However, recombinant human platelet-derived growth factor homodimer BB suppressed BNC responsiveness to IL-1. A recombinant human IL-1 receptor antagonist protein inhibited BNC activation by IL-1 but not TNF alpha.
authors.affiliation: Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Justen
authors.forename: R G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: J E
authors.initials: JE
authors.lastname: Lund
authors.forename: L M
authors.initials: LM
authors.lastname: Sam
mesh_terms: D000818:Animals; D002356:Cartilage / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010450:Endopeptidases / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D018093:Gelatinases; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008666:Metalloendopeptidases; D003012:Microbial Collagenase / Q000096:biosynthesis; D010434:Pepsin A / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide; D010450:Endopeptidases; D010447:Peptide Hydrolases; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; C030895:caseinase; D003012:Microbial Collagenase; D015232:Dinoprostone