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<HTML> <HEAD> <TITLE> TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells -- Takeshita et al. 155 (1): 419 -- The Journal of Immunology</TITLE>  <script language="JavaScript">  </script> <style type="text/css"></style> <style type="text/css"></style>  <script language="javascript">  </script> <script type="text/javascript" src="/javascript/ajax/xmlhttprequest.js"></script> <script type="text/javascript" src="/javascript/ajax/utility.js"></script> <script type="text/javascript" src="/javascript/entrez/callback.js"></script> <meta name="citation_journal_title" content="The Journal of Immunology"> <meta name="citation_publisher" content="Am Assoc Immnol"> <meta name="citation_authors" content="Takeshita, A; Chen, Y; Watanabe, A; Kitano, S; Hanazawa, S"> <meta name="citation_title" content="TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells"> <meta name="citation_date" content="07/01/1995"> <meta name="citation_volume" content="155"> <meta name="citation_issue" content="1"> <meta name="citation_firstpage" content="419"> <meta name="citation_id" content="155/1/419"> <meta name="citation_mjid" content="jimmunol;155/1/419"> <meta name="citation_abstract_html_url" content="http://www.jimmunol.org/cgi/content/abstract/155/1/419"> <meta name="citation_pdf_url" content="http://www.jimmunol.org/cgi/reprint/155/1/419.pdf"> <meta name="citation_pmid" content="7602115"> <meta name="dc.Contributor" content="Takeshita, A"> <meta name="dc.Contributor" content="Chen, Y"> <meta name="dc.Contributor" content="Watanabe, A"> <meta name="dc.Contributor" content="Kitano, S"> <meta name="dc.Contributor" content="Hanazawa, S"> <meta name="dc.Title" content="TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant 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chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells</H2> <P> <STRONG> A Takeshita, Y Chen, A Watanabe, S Kitano and S Hanazawa </STRONG> <BR> <FONT SIZE=-1>Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan.</FONT> <P> In this work, we demonstrate the signal-transducing mechanism of TGF- beta<SUP> </SUP> 1 for gene expression of monocyte chemoattractant JE/monocyte<SUP> </SUP> chemoattractant protein 1 (MCP-1) in clonal osteoblastic MC3T3-E1 cells.<SUP> </SUP> TGF-beta 1-induced JE/MCP-1 gene expression in the cells was inhibited<SUP> </SUP> markedly by H-7 (1-(5-isoguinolinesulfonyl)-2-O-<SUP> </SUP> methylpiperazine-dihydrochloride) and staurosporine, potent inhibitors of<SUP> </SUP> protein kinase. TGF-beta 1-induced expression of both early proto-<SUP> </SUP> oncogenes c-fos and c-jun in the cells was also inhibited by H-7 and<SUP> </SUP> staurosporine. Antisense oligonucleotides to c-fos and c-jun genes<SUP> </SUP> inhibited significantly the cytokine-induced JE/MCP-1 gene expression.<SUP> </SUP> Curcumin, a specific inhibitor of c-jun/AP-1, inhibited the cytokine-<SUP> </SUP> induced c-jun gene expression in a dose-dependent manner, though the c- fos<SUP> </SUP> gene expression was not affected. TGF-beta 1 stimulated transcriptionally<SUP> </SUP> the JE/MCP-1 gene expression, and this stimulation was inhibited<SUP> </SUP> significantly by curcumin. Curcumin-induced inhibition of the JE/MCP-1 gene<SUP> </SUP> product was also evidenced by both an assay involving immunoprecipitation<SUP> </SUP> with antiserum specific for JE/MCP-1 and an assay for monocyte chemotaxis.<SUP> </SUP> Curcumin markedly inhibited AP-1 binding activity to 12-tetradecanoyl<SUP> </SUP> phorbol-13-acetate-responsive element (TRE) in the cytokine-treated cells.<SUP> </SUP> Furthermore, H-7 and staurosporine also inhibited the binding activity to<SUP> </SUP> TRE in the cells treated by the cytokine. These results demonstrate that<SUP> </SUP> TGF-beta 1 induces expression of monocyte chemoattractant JE/MCP-1 via the<SUP> </SUP> transcriptional factor AP- 1 induced by protein kinase in the osteoblastic<SUP> </SUP> cells. </VARDEF> <BR CLEAR=ALL> <FONT FACE=""> </FONT> <BR CLEAR=ALL> <BR CLEAR=ALL> <A NAME="otherarticles"></A> <P><FONT SIZE=+2><STRONG> This article has been cited by other articles:</STRONG></FONT> <P> <TABLE CELLPADDING="0" CELLSPACING="0" BORDER="0" WIDTH="600"> <TR BGCOLOR="#D9D4C5"> <TD ALIGN="CENTER" VALIGN="TOP" WIDTH="25"><IMG ALT="" WIDTH="25" HEIGHT="5" SRC="/icons/spacer.gif"><BR> </TD> <TD WIDTH="5"><IMG ALT="" WIDTH="5" HEIGHT="5" SRC="/icons/spacer.gif"></TD> <TD ALIGN="CENTER" VALIGN="TOP" WIDTH="61" NOWRAP> <A HREF="http://mcb.asm.org"><IMG ALT="Home page" WIDTH="59" HEIGHT="80" VSPACE="5" BORDER="1" SRC="http://mcb.asm.org/portal_imgs/search_result.gif"></A><BR> </TD> <TD WIDTH="5"><IMG ALT="" WIDTH="5" HEIGHT="5" SRC="/icons/spacer.gif"></TD> <TD VALIGN="TOP" WIDTH="499" NOWRAP> <A HREF="http://mcb.asm.org"><IMG ALT="Mol. 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Chem., October 6, 2000; 275(41): 32220 - 32226. <BR> <A HREF="http://www.jbc.org/cgi/content/abstract/275/41/32220">[Abstract]</A> <A HREF="http://www.jbc.org/cgi/content/full/275/41/32220">[Full Text]</A> <A HREF="http://www.jbc.org/cgi/reprint/275/41/32220">[PDF]</A> <BR><IMG ALT="" WIDTH="499" HEIGHT="1" SRC="/icons/spacer.gif"> </FONT></TD> <TD WIDTH="5"><IMG ALT="" WIDTH="5" HEIGHT="5" SRC="/icons/spacer.gif"></TD> </TR> <TR><TD COLSPAN="6"><HR NOSHADE SIZE="1" WIDTH="600" COLOR="#828282" ALIGN="LEFT"></TD></TR> </TABLE> <BR CLEAR=ALL> <BR CLEAR=ALL> <P> <HR NOSHADE ALIGN="LEFT" WIDTH="450" SIZE="1"> <TABLE CELLPADDING="2" CELLSPACING="2" WIDTH="450"> <TR> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">HOME</FONT></A></TD> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/help/"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">HELP</FONT></A></FONT></TD> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/cgi/feedback"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">FEEDBACK</FONT></A></TD> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/subscriptions/"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">SUBSCRIPTIONS</FONT></A></TD> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/contents-by-date.0.shtml"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">ARCHIVE</FONT></A></TD> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/search.dtl"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">SEARCH</FONT></A></TD> <TD ALIGN="CENTER" VALIGN="TOP" BGCOLOR=000099 NOWRAP><A TARGET="_top" STYLE="text-decoration: none" HREF="/content/vol155/issue1/"><FONT SIZE="-2" COLOR="#FFFFFF" FACE="arial,helvetica">TABLE OF CONTENTS</FONT></A></TD> </TR> </TABLE> <FONT SIZE="-2" FACE="arial,helvetica"><A TARGET="_top" HREF="/misc/terms.shtml">This Website Copyright © 1995 by The American Association of Immunologists, Inc. 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