Silica induces nuclear factor-kappaB activation through TAK1 and NIK in Rat2 cell line. 2003

HyeYoung Cho, and JooYong Lee, and Noh-Jin Kwak, and Kweo-Haeng Lee, and SukJoo Rha, and Young-Hoon Kim, and Yong-Yeun Cho, and Ki-Hwa Yang, and KyoungAh Kim, and Young Lim
Department of Occupational and Environmental Medicine, College of Medicine, The Catholic University of Korea, Youngdunpo-gu, Seoul, South Korea.

Silica has been known to be a factor in acute cell injury and chronic pulmonary fibrosis. In Rat2 fibroblasts, silica induced the activation of nuclear factor-kappa B (NF-kappaB), which plays a crucial role in regulating the expression of many genes involved in the subsequent inflammatory response. In addition, we observed that transforming growth factor-beta activated kinase 1 (TAK1) and NF-kappaB-inducing kinase (NIK) were involved in silica-mediated NF-kappaB activation in Rat2 cells. The dominant negative mutant forms of TAK1 and NIK inhibited the silica-induced NF-kappaB activation in Rat2 cells. Furthermore, we demonstrated that endogenous TAK1 is phosphorylated in silica-stimulated Rat2 cells. These results indicate that TAK1 functions as a critical mediator in the silica-induced signaling pathway.

UI MeSH Term Description Entries
D008156 Luciferases Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates. Luciferase
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000097782 NF-kappaB-Inducing Kinase A protein serine-threonine kinase that catalyzes the activation of canonical and non-canonical NF-kappaB pathways. MAP3K14 Kinase,Mitogen-Activated Protein Kinase Kinase Kinase 14,NF-kappa B Kinase,NF-kappa-B-Inducing Kinase (NIK),NFkB Kinase,NIK Protein,Nuclear Factor kappa B Kinase,B Kinase, NF-kappa,Kinase, MAP3K14,Kinase, NF-kappa B,Kinase, NF-kappaB-Inducing,Kinase, NFkB,Mitogen Activated Protein Kinase Kinase Kinase 14,NF kappa B Kinase,NF kappaB Inducing Kinase,Protein, NIK
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012822 Silicon Dioxide Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. Silica,Aerosil,Aerosil 380,Cristobalite,Quso G-32,Quso G32,Tridymite,380, Aerosil,Dioxide, Silicon,G32, Quso,Quso G 32

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