Estrogen receptor β activation inhibits colitis by promoting NLRP6-mediated autophagy
| Autor: | Xiaofei Shen, Xiaona Gao, Wenxian Guan, Guangliang Liu, Wentao Fan, Sarah DeSaeger, Mengcong Li, Marthe De Boevre, Zhangshan Gao, Suquan Song, Shuo Zhang, Liping Yan, Chenchen Ding, Yufan Miao, Shuihui Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
NLRP6
Chemistry Inflammasomes Nucleotides Tumor Necrosis Factor-alpha Autophagy Anti-Inflammatory Agents Estrogen receptor Estrogens NLR Proteins Receptors Cell Surface medicine.disease Colitis General Biochemistry Genetics and Molecular Biology Mice medicine Cancer research Animals Estrogen Receptor beta |
| Zdroj: | Cell reports. 41(2) |
| ISSN: | 2211-1247 |
| Popis: | Estrogen receptor β (ERβ) and NLRP6 are highly expressed in intestinal tissues. Loss of ERβ and NLRP6 exacerbate colitis in mouse models. However, the underlying mechanisms are incompletely understood. Here, we report that ERβ attenuates inflammation by inducing NLRP6-mediated autophagy. Specifically, ERβ directly activates the NLRP6 gene expression via binding to estrogen responsive element (ERE) of Nlrp6 gene promoter. ERβ also physically interacts with the NLRP6 nucleotide-binding domain and promotes NLRP6 inflammasome assembly. The ERβ-NLRP6 axis then interacts with multiple autophagy-related proteins including ULK1, BECN1, ATG16L1, LC3B, p62 to affect the autophagosome biogenesis and control autophagic flux. Finally, NLRP6-mediated autophagy suppresses the inflammatory response by promoting the K48-linked polyubiquitination of ASC, Casp-1 p20, IL-1β, TNF-α, and prohibitin-2. Thus, ERβ-NLRP6 direct an anti-inflammatory response by promoting autophagy. Our work uncovers an ERβ-NLRP6-autophagy pathway as an unrecognized regulatory mechanism that maintains intestinal epithelial cell homeostasis and facilitates tissue repair in colitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|