Interleukin-1 modulates phosphorylation of proteins in human osteoblastic cells
Date
1995
DOI
Authors
Kang, Yung-Ming
Version
OA Version
Citation
Abstract
Local regulation of osseous wound healing is thought to reflect the cumulative response to combinations of growth factors and cytokines present in the bone lesion. The effect of growth factors on bone metabolism is likely to be influenced by pro-inflammatory cytokines. Recent studies have revealed that interleukin-1 (IL-1) may play an important role in pathogenesis of lesions of endodontic origin. Interleukin-1 is an immune cytokine generated in osseous inflammation, stimulates bone resorption and inhibits bone formation. In the present studies, we first investigated and compared the tyrosyl phosphorylation pattern induced by EGF, IGF-1, PDGF-AA and bFGF in human osteoblastic cells. We then examined the modulation of IL-1 on the tyrosyl phosphoproteins induced by each ligand. Immunoblot analyses show EGF, IGF-1 and PDGF-AA each elicit a different pattern of tyrosyl phosphoproteins. The down-regulation of IL-1 on autophosphorylation of these cognate receptors is limited to Mr 180,000 PDGF-[alpha] receptor. Immunoprecipitation experiments suggest this down-regulation might be caused by a decrease in synthesis of PDGF-a receptor. For other ligand-induced tyrosyl phosphoproteins, IL-1 [beta] reduces the intensity of EGF-induced pp55,000, and IGF-1 induced pp185,000 and pp175,000. By a renaturation of blotted protein kinases assay, we have identified a protein kinase complex at Mr 76,000 to 78,000 immediately activated by addition of IL-1 p. A series of experiments were then undertaken to investigate the potential mechanisms that might be involved in IL-[beta] modulation of PDGF-AA tyrosine kinase activity. By using inhibitors of secondary message pathways, we determined that the inhibitory effect of IL-1[beta] on PDGF-AA receptor tyrosyl auto-phosphorylation is not dependent on protein kinase A or protein kinase C. These data suggest the existence of an alternative pathway that may involve other unidentified pathways in IL-1 [beta] signaling.
The existence of bacteria or endotoxin in the root canal system may induce the release of immune cytokines from the periapical microenvironment, such as IL-1, and subsequently enhance bone resorption or inhibit bone formation. In order to achieve a successful endodontic treatment, all bacteria or bacterial products must be eliminated from the root canal system.
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Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1995 (Endodontics).
Includes bibliographic references : leaves 91-125.
Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1995 (Endodontics).
Includes bibliographic references : leaves 91-125.
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This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.