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Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. 总被引:51,自引:14,他引:51 下载免费PDF全文
The promoter region of the interleukin-6 (IL-6) gene has a putative NF-kappa B-binding site. We found that a fragment of the IL-6 promoter containing the site specifically binds highly purified NF-kappa B protein and the NF-kappa B protein in nuclear extracts of phorbol ester-induced Jurkat cells. Mutations of the NF-kappa B site abolished complex formation with both purified NF-kappa B and the nuclear extract protein. Transient expression of chloramphenicol acetyltransferase (CAT) plasmids containing the IL-6 promoter revealed very little activity of the promoter in U-937 monocytic cells and in HeLa cells before stimulation. However, stimulation of U-937 and HeLa cells by inducers of NF-kappa B led to a dramatic increase in CAT activity. Mutations in the NF-kappa B-binding site abolished inducibility of IL-6 promoter-cat constructs in U-937 cells by lipopolysaccharide, tumor necrosis factor alpha, the double-stranded RNA poly(IC), or phytohemagglutinin and in HeLa cells by tumor necrosis factor alpha and drastically reduced but did not completely eliminate inducibility in HeLa cells stimulated by double-stranded RNA poly(IC) or phorbol 12-myristate 13-acetate. These results suggest that NF-kappa B is an important mediator for activation of the IL-6 gene by a variety of IL-6 inducers in both U-937 and HeLa cells and that alternative inducible enhancer elements contribute in a cell-specific manner to IL-6 gene induction. Because NF-kappa B is involved in the control of a variety of genes activated upon inflammation, NF-kappa B may play a central role in the inflammatory response to infection and tissue injury. 相似文献
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Steer JH Kroeger KM Abraham LJ Joyce DA 《The Journal of biological chemistry》2000,275(24):18432-18440
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Diesel exhaust particles induce NF-kappa B activation in human bronchial epithelial cells in vitro: importance in cytokine transcription 总被引:7,自引:0,他引:7
Takizawa H Ohtoshi T Kawasaki S Kohyama T Desaki M Kasama T Kobayashi K Nakahara K Yamamoto K Matsushima K Kudoh S 《Journal of immunology (Baltimore, Md. : 1950)》1999,162(8):4705-4711
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EBV-induced gene 3 transcription is induced by TLR signaling in primary dendritic cells via NF-kappa B activation 总被引:7,自引:0,他引:7
Wirtz S Becker C Fantini MC Nieuwenhuis EE Tubbe I Galle PR Schild HJ Birkenbach M Blumberg RS Neurath MF 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(5):2814-2824
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Leila Parvaneh Salar Bakhtiyari Sattar GorganiFiruzjaee Abolfazl Golestani Bagher Larijani 《Biochemical and biophysical research communications》2010,396(2):467-378
The factors responsible for up-regulation of PTP1B, a negative regulator of insulin signaling, in insulin resistance state are not well understood. We performed a series of experiments in C2C12 muscle cells to determine the role of palmitate and an inflammatory state in regulation of PTP1B. Palmitate (0.75 mM) induced PTP1B mRNA and protein level only at 16 h. The combination of palmitate and macrophages, accompanied by a great increase of TNF-α and IL-6 in the culture media, additively caused a higher level of PTP1B protein levels in the muscle. Higher concentrations of palmitate reduced insulin stimulated glucose uptake in myotubes. A specific inhibitor of PTP1B partly increased insulin stimulated glucose uptake in palmitate treated cells. In conclusion, our results showing the additive influence of palmitate and the inflammatory state in the expression of PTP1B imply the involvement of these factors in the overexpression of PTP1B in insulin resistance state. We further provided the evidence suggesting the mediatory role for PTP1B in palmitate induced insulin resistance in myotubes. 相似文献
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Hirasaka K Nikawa T Yuge L Ishihara I Higashibata A Ishioka N Okubo A Miyashita T Suzue N Ogawa T Oarada M Kishi K 《Biochimica et biophysica acta》2005,1743(1-2):130-140
In this study, we examined effects of the three-dimensional (3D)-clinorotation, a simulated-model of microgravity, on proliferation/differentiation of rat myoblastic L6 cells. Differentiation of L6 cells into myotubes was significantly disturbed in the 3D-clinorotation culture system, although the 3D-clinorotation had no effect on the proliferation. The 3D-clinorotation also suppressed the expression of myogenesis marker proteins, such as myogenin and myosin heavy chain (MHC), at the mRNA level. In association with this reduced differentiation, we found that the 3D-clinorotation prevented accumulation of ubiquitinated proteins, compared with non-rotation control cells. Based on these findings, we focused on the ubiquitin-dependent degradation of I kappa B, a myogenesis inhibitory protein, to clarify the mechanism of this impaired differentiation. A decline in the amount of I kappa B protein in L6 cells was significantly prevented by the rotation, while the amount of the protein in the non-rotated cells decreased along with the differentiation. Furthermore, the 3D-clinorotation reduced the NF-kappaB-binding activity in L6 cells and prevented the ubiquitination of I kappa B proteins in the I kappa B- and ubiquitin-expressing Cos7 cells. Other myogenic regulatory factors, such as deubiquitinases, cyclin E and oxygen, were not associated with the differentiation impaired by the clinorotation. Our present results suggest that simulated microgravity such as the 3D-clinorotation may disturb skeletal muscle cell differentiation, at least in part, by inhibiting the NF-kappa B pathway. 相似文献
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《FEBS letters》1997,403(3):313-317
Proteasomes function mainly in the ATP-dependent degradation of proteins that have been conjugated with ubiquitin. To demonstrate the phosphorylation of proteasomes in plants, we conducted an enzymatic dephosphorylation experiment with a crude extract of rice cultured cells. The results indicated that the C2 subunit of the 20S proteasome is phosphorylated in vivo in cultured cells. An in-gel kinase assay and analysis of phosphoamino acids revealed that the C2 subunit is phosphorylated by a 40-kDa serine/threonine protein kinase, the activity of which is inhibited by heparin, a specific inhibitor of casein kinase II. The catalytic subunit of casein kinase II from Arabidopsis was also able to phosphorylate the C2 subunit. These results suggest that the C2 subunit in rice is probably phosphorylated by casein kinase II. Our demonstration of the phosphorylation of proteasomes in plants suggests that phosphorylation might be involved in the general regulation of the functions of proteasomes.© 1997 Federation of European Biochemical Societies. 相似文献
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Nuclear suppression of mitochondrial defects in cells without the ND6 subunit 总被引:4,自引:0,他引:4 下载免费PDF全文
Deng JH Li Y Park JS Wu J Hu P Lechleiter J Bai Y 《Molecular and cellular biology》2006,26(3):1077-1086
Previously, we characterized a mouse cell line, 4A, carrying a mitochondrial DNA mutation in the subunit for respiratory complex I, NADH dehydrogenase, in the ND6 gene. This mutation abolished the complex I assembly and disrupted the respiratory function of complex I. We now report here that a galactose-resistant clone, 4AR, was isolated from the cells carrying the ND6 mutation. 4AR still contained the homoplasmic mutation, and apparently there was no ND6 protein synthesis, whereas the assembly of other complex I subunits into complex I was recovered. Furthermore, the respiratory activity and mitochondrial membrane potential were fully recovered. To investigate the genetic origin of this compensation, the mitochondrial DNA (mtDNA) from 4AR was transferred to a new nuclear background. The transmitochondrial lines failed to grow in galactose medium. We further transferred mtDNA with a nonsense mutation at the ND5 gene to the 4AR nuclear background, and a suppression for mitochondrial deficiency was observed. Our results suggest that change(s) in the expression of a certain nucleus-encoded factor(s) can compensate for the absence of the ND6 or ND5 subunit. 相似文献