Pro-inflammatory cytokines from Kupffer cells downregulate hepatocyte expression of adrenomedullin binding protein-1 Export

@article{Jacob:2007p126, abstract = {Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late hypodynamic phase. Adrenomedullin (AM), a vasodilatory peptide, inhibits this transition from the early phase to the late phase. Adrenomedullin binding protein-1 (AMBP-1) enhances AM-mediated activities. The decrease of AMBP-1 levels in late sepsis reduces the vascular response to AM and produces the hypodynamic phase. Studies have indicated that the administration of LPS downregulates AMBP-1 production in the liver. Since hepatocytes are the primary source of AMBP-1 biosynthesis in the liver, we employed a co-culture strategy using hepatocyte and Kupffer cells to determine whether LPS directly or by increasing pro-inflammatory cytokines from Kupffer cells downregulates AMBP-1 production. Hepatocytes and Kupffer cells isolated from rats were co-cultured and treated with LPS for 24 h. LPS significantly attenuated AMBP-1 protein expression in a dose-dependent manner. Since AMBP-1 is basically a secretory protein, cell supernatants from co-culture cells treated with LPS were examined for AMBP-1 protein levels. LPS treatment caused a dose related decrease in AMBP-1 protein secretion. Similarly, LPS treatment produced a significant decrease in AMBP-1 protein expression in hepatocytes and Kupffer cells cultured using transwell inserts. LPS had no direct effect on AMBP-1 levels in cultured hepatocytes or Kupffer cells alone. To confirm that the observed effects in co-culture were due to the cytokines released from Kupffer cells, hepatocytes were treated with IL-1beta or TNF-alpha for 24 h and AMBP-1 expression was examined. The results indicated that both cytokines significantly inhibited AMBP-1 protein levels. Thus, pro-inflammatory cytokines released from Kupffer cells are responsible for downregulation of AMBP-1.}, author = {Jacob, Asha and Zhou, Mian and Wu, Rongqian and Halpern, Vivienne J. and Ravikumar, Thanjavur S. and Wang, Ping}, citeulike-article-id = {3046192}, citeulike-linkout-0 = {http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1Y-4NF4F32-1&_user=1029198&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050560&_version=1&_urlVersion=0&_userid=1029198&md5=0dbbc3eb9eef647d5299d3fc18f8ec1d}, citeulike-linkout-1 = {http://dx.doi.org/10.1016/j.bbadis.2007.03.010}, doi = {10.1016/j.bbadis.2007.03.010}, journal = {Biochim Biophys Acta}, keywords = {animals, cells, coculture, complement, cytokines, down-regulation, factor, factor-alpha, file-import-08-07-27, h, hepatocytes, inflammation, interleukin-1, kupffer, mediators, necrosis, rats, sprague-dawley, techniques, tumor}, local-url = {file://localhost/Users/ken/Documents/Papers/2007/Jacob/Biochim\%20Biophys\%20Acta\%202007\%20Jacob.pdf}, month = {Jul}, number = {7}, pages = {766--72}, posted-at = {2008-07-27 14:46:04}, priority = {2}, title = {Pro-inflammatory cytokines from Kupffer cells downregulate hepatocyte expression of adrenomedullin binding protein-1}, url = {http://dx.doi.org/10.1016/j.bbadis.2007.03.010}, volume = {1772}, year = {2007} }

TY - JOUR ID - Jacob:2007p126 L3 - citeulike-article-id:3046192 N2 - Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late hypodynamic phase. Adrenomedullin (AM), a vasodilatory peptide, inhibits this transition from the early phase to the late phase. Adrenomedullin binding protein-1 (AMBP-1) enhances AM-mediated activities. The decrease of AMBP-1 levels in late sepsis reduces the vascular response to AM and produces the hypodynamic phase. Studies have indicated that the administration of LPS downregulates AMBP-1 production in the liver. Since hepatocytes are the primary source of AMBP-1 biosynthesis in the liver, we employed a co-culture strategy using hepatocyte and Kupffer cells to determine whether LPS directly or by increasing pro-inflammatory cytokines from Kupffer cells downregulates AMBP-1 production. Hepatocytes and Kupffer cells isolated from rats were co-cultured and treated with LPS for 24 h. LPS significantly attenuated AMBP-1 protein expression in a dose-dependent manner. Since AMBP-1 is basically a secretory protein, cell supernatants from co-culture cells treated with LPS were examined for AMBP-1 protein levels. LPS treatment caused a dose related decrease in AMBP-1 protein secretion. Similarly, LPS treatment produced a significant decrease in AMBP-1 protein expression in hepatocytes and Kupffer cells cultured using transwell inserts. LPS had no direct effect on AMBP-1 levels in cultured hepatocytes or Kupffer cells alone. To confirm that the observed effects in co-culture were due to the cytokines released from Kupffer cells, hepatocytes were treated with IL-1beta or TNF-alpha for 24 h and AMBP-1 expression was examined. The results indicated that both cytokines significantly inhibited AMBP-1 protein levels. Thus, pro-inflammatory cytokines released from Kupffer cells are responsible for downregulation of AMBP-1. IS - 7 JF - Biochim Biophys Acta EP - 72 TI - Pro-inflammatory cytokines from Kupffer cells downregulate hepatocyte expression of adrenomedullin binding protein-1 VL - 1772 SP - 766 KW - animals KW - cells KW - coculture KW - complement KW - cytokines KW - down-regulation KW - factor KW - factor-alpha KW - file-import-08-07-27 KW - h KW - hepatocytes KW - inflammation KW - interleukin-1 KW - kupffer KW - mediators KW - necrosis KW - rats KW - sprague-dawley KW - techniques KW - tumor AU - Jacob, Asha AU - Zhou, Mian AU - Wu, Rongqian AU - Halpern, Vivienne AU - Ravikumar, Thanjavur AU - Wang, Ping PY - 2007/Jul// UR - http://dx.doi.org/10.1016/j.bbadis.2007.03.010 ER -