Year: 2016
Type: article
Abstract: Toll-like receptor-mediated NF-κB activation is a major innate immune reaction of vascular endothelial cells (ECs) in response to prooxidative and proinflammatory stimuli. We identified that TNF-α receptor-associated factor-interacting protein with a forkhead-associated domain (TIFA) is a regulator of priming (signal 1) and activating (signal 2) signals of nucleotide oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome in ECs. Oxidative and inflammatory stresses such as atheroprone flow and hyperlipidemia induce and activate TIFA in vitro and in vivo. For the priming of signal 1, sterol regulatory element-binding protein 2 transactivates TIFA, which in turn induces NF-κB activation and augments the transcription of NLRP3 inflammasome components. For the activation of signal 2, Akt is involved in TIFA Thr9 phosphorylation, which is essential for TIFA-TIFA homophilic oligomerization. Thr9 phosphorylation-dependent TIFA oligomerization facilitates the higher-order assembly of NLRP3 inflammasome, as indicated by the interaction between TIFA and caspase-1 in the activated ECs. Our results suggest that TIFA is a crucial mediator in the endothelial innate immune response by potentiating and amplifying NLRP3 inflammasome via augmenting signals 1 and 2.
Authors: Ting-Yang Lin, Tong-You Wade Wei, Shuai Li, Shen-Chih Wang, Ming He, Marcy Martin, Jiao Zhang, Tzu-Pin Shentu, Han Xiao, Jian Kang, Kuei-Chun Wang, Zhen Chen, Shu Chien, Ming-Daw Tsai, John Y.-J. Shyy
Institutions: National Taiwan University, University of California San Diego, Institute of Biological Chemistry, Academia Sinica, Academia Sinica, Tianjin Medical University Cancer Institute and Hospital, Taipei Veterans General Hospital, The University of Texas MD Anderson Cancer Center, University of Alabama at Birmingham, University of California, Riverside, First Affiliated Hospital of Xi'an Jiaotong University, Peking University Third Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1265029905, Flow Regulation of YAP/TAZ in Atherogenesis and Therapeutic Development, Hypoxia-Suppressed Dicer and AGO1 Promote Angiogenesis, Systems Biology Analyses for Hemodynamic Regulation of Vascular Homeostasis, Flow Regulation of YAP/TAZ in Atherogenesis and Therapeutic Development, G6910566751, G7979312748
OpenAlex ID: W2561864182