CARMA3/Bcl10/MALT1-dependent NF-κB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells

• DOI: 10.1073/pnas.0601947103
• Publication Date: 2006-11-14T01:38:56Z
• Authors: Linda M. McAllist...; Jürgen Ruland; Katy Siu; Xiaohong Jin; Shufang Gu; David S. L. Kim; Peter Kuffa; Dawn Kohrt; Tak W. Mak; Gabriel Nuñez; Peter C. Lucas
• Keywords: Proinflammatory cytokine; IκB kinase

Angiotensin II (Ang II) is a peptide hormone that, like many cytokines, acts as proinflammatory agent and growth factor. After injury to the liver, assists in tissue repair by stimulating hepatocytes hepatic stellate cells synthesize extracellular matrix proteins secrete secondary cytokines myofibroblasts proliferate. However, under conditions of chronic liver injury, all these effects conspire promote pathologic fibrosis. Much this effect Ang results from activation NF-kappaB transcription factor response stimulation type 1 receptor, G protein-coupled receptor. Here, we characterize previously undescribed signaling pathway mediating II-dependent NF-kappaB, which composed three principal proteins, CARMA3, Bcl10, MALT1. Blocking function any through use either dominant-negative mutants, RNAi, or gene targeting, effectively abolishes hepatocytes. In addition, Bcl10(-/-) mice show defective cytokine production after treatment. Evidence also presented that activates ubiquitination IKKgamma, regulatory subunit IkappaB kinase complex. These elucidate concrete series molecular events link ligand receptor findings uncover CARMA, MALT1 outside immune system.