HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Franchimont, N. Articles by Canalis, E. Search for Related Content PubMed PubMed Citation Articles by Franchimont, N. Articles by Canalis, E. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 10, 6783-6789, March 5, 1999

Platelet-derived Growth Factor Induces Interleukin-6 Transcription in Osteoblasts through the Activator Protein-1 Complex and Activating Transcription Factor-2

Nathalie Franchimont, Deena Durant, Sheila Rydziel, and Ernesto Canalis^¶

From the  Departments of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105 and the ^¶ University of Connecticut School of Medicine, Farmington, Connecticut 06030

Platelet-derived growth factor (PDGF) BB, a mitogen that stimulates bone resorption, increases the expression of interleukin-6 (IL-6), a cytokine that induces osteoclast recruitment. The mechanisms involved in IL-6 induction by PDGF BB are poorly understood. We examined the effect of PDGF BB on IL-6 expression in cultures of osteoblasts from fetal rat calvariae (Ob cells). PDGF BB increased IL-6 mRNA and heterogeneous nuclear RNA levels, the rate of transcription, and the activity of base pairs (bp) 2906 to +20 IL-6 promoter fragments transiently transfected into Ob cells. Deletion analysis revealed two responsive regions, one containing an activator protein-1 (AP-1) site located between bp 276 and 257, and a second, less well defined, downstream of 257. Targeted mutations of a cyclic AMP-responsive element (CRE), and nuclear factor-IL-6 and nuclear factor-B binding sites in a bp 257 to +20 IL-6 construct that was transfected into Ob cells, revealed that the CRE also contributed to IL-6 promoter induction by PDGF BB. Electrophoretic mobility shift assay revealed AP-1 and CRE nuclear protein complexes that were enhanced by PDGF BB. Supershift assays revealed binding of Jun and Fos to AP-1 and CRE sequences and binding of activating transcription factor-2 to CRE. In conclusion, PDGF BB induces IL-6 transcription in osteoblasts by regulating nuclear proteins of the AP-1 complex and activating transcription factor-2.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				Y. Fukaya, H. Shimada, L.-C. Wang, E. Zandi, and Y. A. DeClerck Identification of Galectin-3-binding Protein as a Factor Secreted by Tumor Cells That Stimulates Interleukin-6 Expression in the Bone Marrow Stroma J. Biol. Chem., July 4, 2008; 283(27): 18573 - 18581. [Abstract] [Full Text] [PDF]

				J. O. Hollinger, C. E. Hart, S. N. Hirsch, S. Lynch, and G. E. Friedlaender Recombinant Human Platelet-Derived Growth Factor: Biology and Clinical Applications J. Bone Joint Surg. Am., February 1, 2008; 90(Supplement_1): 48 - 54. [Abstract] [Full Text] [PDF]

				S. Inouye, M. Fujimoto, T. Nakamura, E. Takaki, N. Hayashida, T. Hai, and A. Nakai Heat Shock Transcription Factor 1 Opens Chromatin Structure of Interleukin-6 Promoter to Facilitate Binding of an Activator or a Repressor J. Biol. Chem., November 9, 2007; 282(45): 33210 - 33217. [Abstract] [Full Text] [PDF]

				K. E. Broderick, T. Zhang, H. Rangaswami, Y. Zeng, X. Zhao, G. R. Boss, and R. B. Pilz Guanosine 3',5'-Cyclic Monophosphate (cGMP)/cGMP-Dependent Protein Kinase Induce Interleukin-6 Transcription in Osteoblasts Mol. Endocrinol., May 1, 2007; 21(5): 1148 - 1162. [Abstract] [Full Text] [PDF]

				H. Takanaga, T. Yoshitake, S. Hara, C. Yamasaki, and M. Kunimoto cAMP-induced Astrocytic Differentiation of C6 Glioma Cells Is Mediated by Autocrine Interleukin-6 J. Biol. Chem., April 9, 2004; 279(15): 15441 - 15447. [Abstract] [Full Text] [PDF]

				P. Monje, M. J. Marinissen, and J. S. Gutkind Phosphorylation of the Carboxyl-Terminal Transactivation Domain of c-Fos by Extracellular Signal-Regulated Kinase Mediates the Transcriptional Activation of AP-1 and Cellular Transformation Induced by Platelet-Derived Growth Factor Mol. Cell. Biol., October 1, 2003; 23(19): 7030 - 7043. [Abstract] [Full Text] [PDF]

				K. S. J. Elenitoba-Johnson, S. D. Jenson, R. T. Abbott, R. A. Palais, S. D. Bohling, Z. Lin, S. Tripp, P. J. Shami, L. Y. Wang, R. W. Coupland, et al. Involvement of multiple signaling pathways in follicular lymphoma transformation: p38-mitogen-activated protein kinase as a target for therapy PNAS, June 10, 2003; 100(12): 7259 - 7264. [Abstract] [Full Text] [PDF]

				J.-J. Ventura, N. J. Kennedy, J. A. Lamb, R. A. Flavell, and R. J. Davis c-Jun NH2-Terminal Kinase Is Essential for the Regulation of AP-1 by Tumor Necrosis Factor Mol. Cell. Biol., April 15, 2003; 23(8): 2871 - 2882. [Abstract] [Full Text] [PDF]

				C. Guillen, P. Martinez, A. R. de Gortazar, M. E. Martinez, and P. Esbrit Both N- and C-terminal Domains of Parathyroid Hormone-related Protein Increase Interleukin-6 by Nuclear Factor-kappa B Activation in Osteoblastic Cells J. Biol. Chem., July 26, 2002; 277(31): 28109 - 28117. [Abstract] [Full Text] [PDF]

				J. Mann, F. Oakley, P. W. M. Johnson, and D. A. Mann CD40 Induces Interleukin-6 Gene Transcription in Dendritic Cells. REGULATION BY TRAF2, AP-1, NF-kappa B, AND CBF1 J. Biol. Chem., May 3, 2002; 277(19): 17125 - 17138. [Abstract] [Full Text] [PDF]

				I. Kosmidou, T. Vassilakopoulos, A. Xagorari, S. Zakynthinos, A. Papapetropoulos, and C. Roussos Production of Interleukin-6 by Skeletal Myotubes . Role of Reactive Oxygen Species Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 587 - 593. [Abstract] [Full Text] [PDF]

				S.J. Webb, J.R. McPherson, K. Pahan, and S. Koka Regulation of TNF-{alpha}-induced IL-6 Production in MG-63 Human Osteoblast-like Cells J. Dent. Res., January 1, 2002; 81(1): 17 - 22. [Abstract] [Full Text] [PDF]

				J. K. Ellington, A. Elhofy, K. L. Bost, and M. C. Hudson Involvement of Mitogen-Activated Protein Kinase Pathways in Staphylococcus aureus Invasion of Normal Osteoblasts Infect. Immun., September 1, 2001; 69(9): 5235 - 5242. [Abstract] [Full Text] [PDF]

				A. M. Reimold, J. Kim, R. Finberg, and L. H. Glimcher Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice Int. Immunol., February 1, 2001; 13(2): 241 - 248. [Abstract] [Full Text] [PDF]

				I. R. Pela, M. E. S. Ferreira, M. C. C. Melo, C. A. A. Silva, M. M. Coelho, and C. F. Valenzuela Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1275 - R1281. [Abstract] [Full Text] [PDF]

				S. C. Manolagas Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis Endocr. Rev., April 1, 2000; 21(2): 115 - 137. [Abstract] [Full Text]

				W. Durante, K. J. Peyton, and A. I. Schafer Platelet-Derived Growth Factor Stimulates Heme Oxygenase-1 Gene Expression and Carbon Monoxide Production in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., November 1, 1999; 19(11): 2666 - 2672. [Abstract] [Full Text] [PDF]

				M. Mesri and D. C. Altieri Leukocyte Microparticles Stimulate Endothelial Cell Cytokine Release and Tissue Factor Induction in a JNK1 Signaling Pathway J. Biol. Chem., August 13, 1999; 274(33): 23111 - 23118. [Abstract] [Full Text] [PDF]

				D. E. Smart, K. J. Vincent, M. J. P. Arthur, O. Eickelberg, M. Castellazzi, J. Mann, and D. A. Mann JunD Regulates Transcription of the Tissue Inhibitor of Metalloproteinases-1 and Interleukin-6 Genes in Activated Hepatic Stellate Cells J. Biol. Chem., June 22, 2001; 276(26): 24414 - 24421. [Abstract] [Full Text] [PDF]