Ctenopharyngodon idella Tollip regulates MyD88-induced NF-κB activation. (October 2021)

• Record Type: Journal Article
• Authors: Wu, Chuxin; Deng, Hang; Li, Dongming; Fan, Lihua; Yao, Dong; Zhi, Xiaoping; Mao, Huiling; Hu, Chengyu
• Is Part Of: Developmental and comparative immunology. Volume 123(2021)
• Publication Date: 2021-10
• Subjects: Tollip -- MyD88 -- Regulate -- NF-κB -- LPS -- Grass carp; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2021.104162
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: Toll-interacting protein (Tollip) and MyD88 are key components of the TLR/IL-1R signaling pathway in mammals. MyD88 is known as a universal adaptor protein involving in TLR/IL-1R-induced NF-κB activation. Tollip is a crucial negative regulator of TLR-mediated innate immune responses. Previous studies have demonstrated that teleost Tollip served as a negative regulator of MyD88-dependent TLR signaling pathway. However, the mechanism is still unclear. In particular, the effect of TBD, C2, and CUE domains of Tollip on MyD88-NF-κB signaling pathway remains to be elucidated. In this study, we found that the response of grass carp Tollip ( Ci Tollip) to LPS stimulation was faster and stronger than that of poly I:C treatment, and Ci Tollip diminished the expression of tnf-α induced by LPS. Further assays indicated that except for the truncated mutant of △CUE2 (1–173 aa), wild type Ci Tollip and other truncated mutants (△N-(52–276 aa), △C2-(173–276 aa) and △CUE1-(1–231 aa)) could associate with MyD88 and negatively regulate MyD88-induced NF-κB activation. It suggested that the C-terminal (173–276 aa), in particular the connection section between C2 and CUE domains (173–231 aa), played a pivotal role in suppressing MyD88-induced activation of NF-κB. Highlights: The response of Ci Tollip to LPS stimulation is faster and stronger than that of poly I:C treatment. Ci Tollip diminishes the expression of TNF-α induced by LPS. Except △CUE2, Ci Tollip and other mutants can associate with MyD88 and negatively regulate MyD88-induced NF-κB activation. Either wild type Ci Tollip or the truncated mutants can form homodimmer.