title: Protein kinase C modulates the amounts of IL-1 receptor mRNA in human lung fibroblasts.
abstract: IL-1 activates human lung fibroblasts via IL-1-specific membrane receptors. The numbers of IL-1 binding sites on fibroblasts are increased after exposure to prostaglandin E2 (PGE2) or IL-1. Increases in binding sites are associated with changes in functional responses to IL-1. In these studies, we determined if alterations in numbers of IL-1 binding sites on human lung fibroblasts were associated with parallel changes in IL-1R mRNA. In addition, since IL-1 and PGE2 can activate protein kinase C (PKC) and protein kinase A (PKA), we exposed human lung fibroblasts to 1-(5-Isoquinoline sulfonyl)-2-methylpiperafine (H7) or staurosporine, which are relatively specific inhibitors of PKC, and N-[2-(methylamino)ethyl]-5-isoquinolinesulfomamide (H8), an inhibitor of PKA, to determine whether the IL-1 and PGE2 stimulated increases in binding sites were mediated by activation of PKC or PKA. H7 decreased the base line and PGE2-stimulated increases in numbers of IL-1 binding sites. Exposure of the fibroblasts to phorbol-12-myristate-13-acetate (PMA) for 24 h, which is known to deplete PKC, also decreased the numbers of base line IL-1 binding sites. These changes were paralleled by changes in amounts of IL-1R mRNA. H7 and staurosporine also blocked IL-1 and PGE2 stimulated increases in IL-1R mRNA. In contrast, H8 had no effect on the base line or PGE2-stimulated increases in numbers of IL-1 binding sites nor did it change the amounts of IL-1R mRNA. These studies show that changes in the numbers of IL-1 binding sites on human lung fibroblasts are paralleled by changes in IL-1R mRNA. In addition, PKC activity is necessary for the expression of both base line and stimulated increases in IL-1 binding sites and IL-1R mRNA. These studies suggest that PKC activity plays an important role in the modulation of IL-1R expression.
authors.affiliation: Department of Internal Medicine, Department of Veterans Affairs, Iowa City, IA 52242.
authors.forename: T R
authors.initials: TR
authors.lastname: Aksamit
authors.forename: M M
authors.initials: MM
authors.lastname: Monick
authors.forename: G W
authors.initials: GW
authors.lastname: Hunninghake
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002460:Cell Line; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008168:Lung / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics*
chemical_list: D007375:Interleukin-1; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D015232:Dinoprostone