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This soluble pattern\u2010recognition molecule is present in high concentrations in serum and represents an important defense mechanism of the host. Regulation of the hepatic acute\u2010phase response and its termination are important mechanisms for limiting systemic inflammatory activity of the host organism. We show here that TGF\u2010\u03b21, in a dose\u2010dependent fashion, is able to inhibit LBP transcript accumulation and LBP protein synthesis induced by IL\u20106, IL\u20101\u03b2 and dexamethasone in hepatoma cell lines. These data were confirmed employing primary human hepatocytes, where TGF\u2010\u03b21 also inhibited LBP protein synthesis. We identified and analyzed several Smad\u2010binding sites (Smads are major regulatory elements of TGF\u2010\u03b21) within the LBP promoter, and found that one of them was active. We furthermore identified an AP\u20101\u2010binding site clearly conferring inhibitory effects of TGF\u2010\u03b21 towards LBP promoter activity, shown by gel shift and promoter mutagenesis experiments. Further elucidating the mechanism of transcriptional regulation of proteins involved in innate immune responses may potentially help to develop novel intervention strategies for the acute\u2010phase response, sepsis, and septic shock.<\/jats:p>","DOI":"10.1002\/eji.200324874","type":"journal-article","created":{"date-parts":[[2004,4,5]],"date-time":"2004-04-05T13:02:42Z","timestamp":1081170162000},"page":"1441-1450","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of hepatic transcriptional induction of lipopolysaccharide\u2010binding protein by transforming\u2010growth\u2010factor \u03b21"],"prefix":"10.1002","volume":"34","author":[{"given":"Werner","family":"Hallatschek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gesa","family":"Fiedler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten\u2004J.","family":"Kirschning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e4nzi","family":"Creutzburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Lamping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"N\u00fcssler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf\u2004R.","family":"Schumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,4,22]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90137-6"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902113400607"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"8477","DOI":"10.1016\/S0021-9258(17)37218-6","article-title":"Lipopolysaccharide binding protein expression in primary human hepatocytes and HepG2 hepatoma cells.","volume":"269","author":"Grube B. 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