Up-regulation of IL-1 receptor through PI3K/Akt is essential for the induction of iNOS gene expression in hepatocytes. Export

@article{citeulike:3474705, abstract = {BACKGROUND/AIMS: Nuclear translocation and DNA binding of NF-kappaB is essential, as interleukin-1beta (IL-1beta) stimulates the induction of inducible nitric oxide synthase (iNOS) gene expression in hepatocytes. However, recent evidence indicates that the activation of NF-kappaB is not sufficient to induce the NF-kappaB-dependent transcription, and the existence of a second signaling is postulated. METHODS: Primary cultured hepatocytes were treated with IL-1beta, and the expression of iNOS and type 1 IL-1 receptor (IL-1R1) was analyzed in the presence of antisense of IL-1R1, phosphatidylinositol 3-kinase (PI3K) inhibitor, proteasome inhibitor and hypoxia. Moreover, the activities of Akt and NF-kappaB were recorded and the cotransfection was carried out. RESULTS: Antisense experiment revealed that IL-1R1 was required for iNOS transcription. IL-1beta markedly stimulated the induction of IL-1R1, which preceded the induction of iNOS. The IL-1R1 induction was found to be PI3K/Akt-dependent but NF-kappaB-independent. The up-regulation of IL-1R1 was associated with the second activation of Akt, which accelerated the phosphorylation of NF-kappaB p65 subunit. Cotransfection experiments revealed that Akt increased the transcriptional activity of iNOS gene promoter. CONCLUSIONS: These results indicate that the up-regulation of IL-1R1 in concert with the activation of NF-kappaB is required for the transcriptional activation of iNOS gene.}, author = {Teshima, S. and Nakanishi, H. and Nishizawa, M. and Kitagawa, K. and Kaibori, M. and Yamada, M. and Habara, K. and Kwon, A. H. and Kamiyama, Y. and Ito, S. and Okumura, T.}, citeulike-article-id = {3474705}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jhep.2003.12.018}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15030977}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15030977}, doi = {10.1016/j.jhep.2003.12.018}, issn = {0168-8278}, journal = {Journal of hepatology}, keywords = {hepatocytes, il-1r1, inos, pi3kakt}, month = {April}, number = {4}, pages = {616--623}, posted-at = {2008-11-03 13:04:22}, priority = {3}, title = {Up-regulation of IL-1 receptor through PI3K/Akt is essential for the induction of iNOS gene expression in hepatocytes.}, url = {http://dx.doi.org/10.1016/j.jhep.2003.12.018}, volume = {40}, year = {2004} }

TY - JOUR ID - citeulike:3474705 L3 - citeulike-article-id:3474705 N2 - BACKGROUND/AIMS: Nuclear translocation and DNA binding of NF-kappaB is essential, as interleukin-1beta (IL-1beta) stimulates the induction of inducible nitric oxide synthase (iNOS) gene expression in hepatocytes. However, recent evidence indicates that the activation of NF-kappaB is not sufficient to induce the NF-kappaB-dependent transcription, and the existence of a second signaling is postulated. METHODS: Primary cultured hepatocytes were treated with IL-1beta, and the expression of iNOS and type 1 IL-1 receptor (IL-1R1) was analyzed in the presence of antisense of IL-1R1, phosphatidylinositol 3-kinase (PI3K) inhibitor, proteasome inhibitor and hypoxia. Moreover, the activities of Akt and NF-kappaB were recorded and the cotransfection was carried out. RESULTS: Antisense experiment revealed that IL-1R1 was required for iNOS transcription. IL-1beta markedly stimulated the induction of IL-1R1, which preceded the induction of iNOS. The IL-1R1 induction was found to be PI3K/Akt-dependent but NF-kappaB-independent. The up-regulation of IL-1R1 was associated with the second activation of Akt, which accelerated the phosphorylation of NF-kappaB p65 subunit. Cotransfection experiments revealed that Akt increased the transcriptional activity of iNOS gene promoter. CONCLUSIONS: These results indicate that the up-regulation of IL-1R1 in concert with the activation of NF-kappaB is required for the transcriptional activation of iNOS gene. IS - 4 JF - Journal of hepatology SN - 0168-8278 EP - 623 TI - Up-regulation of IL-1 receptor through PI3K/Akt is essential for the induction of iNOS gene expression in hepatocytes. VL - 40 SP - 616 KW - hepatocytes KW - il-1r1 KW - inos KW - pi3kakt AU - Teshima, S AU - Nakanishi, H AU - Nishizawa, M AU - Kitagawa, K AU - Kaibori, M AU - Yamada, M AU - Habara, K AU - Kwon, AH AU - Kamiyama, Y AU - Ito, S AU - Okumura, T PY - 2004/04// UR - http://dx.doi.org/10.1016/j.jhep.2003.12.018 ER -