scholarly journals Estrogen Receptor β Activation Inhibits Colitis by Promoting NLRP6-Mediated Autophagy

Author(s):  
Wentao Fan ◽  
Chenchen Ding ◽  
Shuihui Liu ◽  
Xiaona Gao ◽  
Xiaofei Shen ◽  
...  

Abstract 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.

1995 ◽  
Vol 15 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Y Le Dréan ◽  
G Lazennec ◽  
L Kern ◽  
D Saligaut ◽  
F Pakdel ◽  
...  

ABSTRACT We previously reported that the expression of the rainbow trout estrogen receptor (rtER) gene is markedly increased by estradiol (E2). In this paper, we have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyl transferase (CAT), linked to 5′ flanking regions of the rtER gene promoter, to identify cis-elements responsible for E2 inducibility. Deletion analysis localized an estrogen-responsive element (ERE), at position +242, with one mutation on the first base compared with the consensus sequence. This element confers estrogen responsiveness to CAT reporter linked to both the herpes simplex virus thymidine kinase promoter and the homologous rtER promoter. Moreover, using a 0·2 kb fragment of the rtER promoter encompassing the ERE and the rtER DNA binding domain obtained from a bacterial expression system, DNase I footprinting experiments demonstrated a specific protection covering 20 bp (+240/+260) containing the ERE sequence. Based on these studies, we believe that this ERE sequence, identified in the rtER gene promoter, may be a major cis-acting element involved in the regulation of the gene by estrogen.


1988 ◽  
Vol 16 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Ludger Klein-Hitpass ◽  
Gerhart U. Ryffel ◽  
Ellen Heitlinger ◽  
Andrew C.B. Cato

1991 ◽  
Vol 5 (4) ◽  
pp. 555-563 ◽  
Author(s):  
Nicola Medici ◽  
Vincenzo Nigro ◽  
Ciro Abbondanza ◽  
Bruno Moncharmont ◽  
Anna Maria Molinari ◽  
...  

2010 ◽  
Vol 12 (3) ◽  
pp. R101 ◽  
Author(s):  
John Dulos ◽  
Peter Vijn ◽  
Cindy van Doorn ◽  
Claudia L Hofstra ◽  
Desiree Veening-Griffioen ◽  
...  

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