title: Inflammatory cytokines (IL-1alpha, TNF-alpha) and LPS modulate the Ca2+ signaling pathway in osteoblasts.
abstract: Locally derived growth factors and cytokines in bone play a crucial role in the regulation of bone remodeling, i.e., bone formation and bone resorption processes. We studied the effect of interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, and Escherichia coli lipopolysaccharide (LPS) on the hormone-activated Ca2+ message system in the osteoblastic cell line UMR-106 and in osteoblastic cultures derived from neonatal rat calvariae. In both cell preparations, IL-1alpha, TNF-alpha, and LPS did not alter basal intracellular Ca2+ concentration ([Ca2+]i) but attenuated Ca2+ transients evoked by parathyroid hormone (PTH) and PGE2 in a dose (1-100 ng/ml)- and time (8-24 h)-dependent fashion. The cytokines modulated hormonally induced Ca2+ influx (estimated by using Mn2+ as a surrogate for Ca2+) as well as Ca2+ mobilization from intracellular stores. The latter was linked to suppressed production of hormonally induced inositol 1,4,5-trisphosphate. The effect of cytokines on [Ca2+]i was abolished by the tyrosine kinase inhibitor herbimycin A (50 ng/ml). The cytokine's effect was, however, independent of nitric oxide (NO) production, since NO donors (sodium nitroprusside) as well as permeable cGMP analogs augment, rather than attenuate, hormonally induced Ca2+ transients in osteoblasts. Given the stimulatory role of cytokines on NO production in osteoblasts, the disparate effects of cytokines and NO on the Ca2+ signaling pathway may serve an autocrine/paracrine mechanism for modulating the effect of calciotropic hormones on bone metabolism.
authors.affiliation: Laboratory of Membrane Biology, Research Institute, Division of Nephrology and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Tam
authors.forename: S
authors.initials: S
authors.lastname: Schotland
authors.forename: J
authors.initials: J
authors.lastname: Green
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D007375:Interleukin-1 / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D010716:Phosphatidylinositols; D011809:Quinones; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; D009569:Nitric Oxide; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone; D002118:Calcium