Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1 beta in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity.
Recombinant human interleukin-1 beta, a mediator of osteoblastic cell function, was found to regulate the expression of the cell adhesion receptors, integrins, on human osteosarcoma cells. Interleukin-1 beta (IL-1 beta) at picomolar concentrations, specifically elevated approximately six- to tenfold the expression of the beta 1 subunit and its associated alpha subunits, but not the related vitronectin receptor, within 20 hours. Integrin beta 1 messenger RNA levels were elevated within 6 hours and peaked to tenfold higher levels after 20 hours exposure to IL-1 beta in two human osteosarcoma cell lines. The increase in the cell-surface beta 1 integrins resulted in a stronger binding of the IL-1 beta-treated cells to fibronectin. Cell growth was also inhibited by IL-1 beta, cell morphology was altered, and IL-1 beta-treated cells expressed an approximately two- to threefold higher alkaline phosphatase. This increase in alkaline phosphatase activity was found to be independent of the inhibition of cell proliferation. These data indicate that the beta 1 integrin family of cell surface receptors is a target for regulation by IL-1 beta, which also regulates cell proliferation and the expression of the osteoblastic phenotype in human osteosarcoma cells.
Dedhar
S
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Department of Advanced Therapeutics, Cancer Control Agency of British Columbia, Canada.
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D016023:Integrins; D007375:Interleukin-1 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D016023:Integrins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D000469:Alkaline Phosphatase