Adenoviral gene delivery can inactivate Kupffer cells: role of oxidants in NF-kappaB activation and cytokine production Export

@article{citeulike:4862775, abstract = {Kupffer cells play a significant role in the pathogenesis of several liver diseases; therefore, a potential therapeutic strategy would be to inactivate the Kupffer cell with a gene-delivery system. Although recombinant adenovirus provides robust, transgene expression in parenchymal cells, whether adenovirus transduces Kupffer cells is unclear. Thus, the purpose of this study was to evaluate this possibility. In animals infected with adenovirus, Kupffer cells were identified positively to express adenoviral transgenes by immunohistochemical techniques and Western blot analysis, indicating that Kupffer cells are transduced in vivo. Indeed, isolated Kupffer cells were transduced in vitro with recombinant adenovirus in a dose-dependent manner. Moreover, adenoviral transduction of Kupffer cells was blocked by inhibitors of {alpha}V{beta}5 integrin, the co-receptor for adenovirus binding, supporting the hypothesis that adenovirus transduces Kupffer cells via an {alpha}V{beta}5 integrin-dependent mechanism. Indeed, it is shown here that Kupffer cells express {alpha}V{beta}5 integrins. In a functional assay, infection of isolated Kupffer cells with adenovirus containing superoxide dismutase or I{kappa}B{alpha} super-repressor blunted LPS-induced nuclear transcription factor kappa B (NF-{kappa}B) activation and tumor necrosis factor {alpha} (TNF-{alpha}) production but not IL-10 production. Moreover, superoxide production was blocked by expression of superoxide dismutase. These data support the hypothesis that LPS-induced NF-{kappa}B activation and TNF-{alpha} production in Kupffer cells are oxidant-dependent. These findings suggest that Kupffer cell-targeted approaches may be a potential therapeutic strategy against many inflammatory diseases including early alcohol-induced liver injury.}, author = {Wheeler, Michael D. and Yamashina, Shunhei and Froh, Matthias and Rusyn, Ivan and Thurman, Ronald G.}, citeulike-article-id = {4862775}, citeulike-linkout-0 = {http://www.jleukbio.org/cgi/content/abstract/69/4/622}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11310849}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11310849}, day = {1}, journal = {J Leukoc Biol}, keywords = {adenovirus, cre, kupffer, track, tracking}, month = {April}, number = {4}, pages = {622--630}, posted-at = {2009-06-15 23:40:05}, priority = {2}, title = {Adenoviral gene delivery can inactivate Kupffer cells: role of oxidants in NF-{kappa}B activation and cytokine production}, url = {http://www.jleukbio.org/cgi/content/abstract/69/4/622}, volume = {69}, year = {2001} }

TY - JOUR ID - citeulike:4862775 L3 - citeulike-article-id:4862775 N2 - Kupffer cells play a significant role in the pathogenesis of several liver diseases; therefore, a potential therapeutic strategy would be to inactivate the Kupffer cell with a gene-delivery system. Although recombinant adenovirus provides robust, transgene expression in parenchymal cells, whether adenovirus transduces Kupffer cells is unclear. Thus, the purpose of this study was to evaluate this possibility. In animals infected with adenovirus, Kupffer cells were identified positively to express adenoviral transgenes by immunohistochemical techniques and Western blot analysis, indicating that Kupffer cells are transduced in vivo. Indeed, isolated Kupffer cells were transduced in vitro with recombinant adenovirus in a dose-dependent manner. Moreover, adenoviral transduction of Kupffer cells was blocked by inhibitors of {alpha}V{beta}5 integrin, the co-receptor for adenovirus binding, supporting the hypothesis that adenovirus transduces Kupffer cells via an {alpha}V{beta}5 integrin-dependent mechanism. Indeed, it is shown here that Kupffer cells express {alpha}V{beta}5 integrins. In a functional assay, infection of isolated Kupffer cells with adenovirus containing superoxide dismutase or I{kappa}B{alpha} super-repressor blunted LPS-induced nuclear transcription factor kappa B (NF-{kappa}B) activation and tumor necrosis factor {alpha} (TNF-{alpha}) production but not IL-10 production. Moreover, superoxide production was blocked by expression of superoxide dismutase. These data support the hypothesis that LPS-induced NF-{kappa}B activation and TNF-{alpha} production in Kupffer cells are oxidant-dependent. These findings suggest that Kupffer cell-targeted approaches may be a potential therapeutic strategy against many inflammatory diseases including early alcohol-induced liver injury. IS - 4 JF - J Leukoc Biol EP - 630 TI - Adenoviral gene delivery can inactivate Kupffer cells: role of oxidants in NF-{kappa}B activation and cytokine production VL - 69 SP - 622 KW - adenovirus KW - cre KW - kupffer KW - track KW - tracking AU - Wheeler, Michael AU - Yamashina, Shunhei AU - Froh, Matthias AU - Rusyn, Ivan AU - Thurman, Ronald PY - 2001/04/01/ UR - http://www.jleukbio.org/cgi/content/abstract/69/4/622 ER -