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Estrogen receptor beta (ERβ) activation plays a therapeutic role in murine models of inflammatory bowel disease (IBD) via inhibiting P2X3 and P2X7 receptors
Author(s) -
Ma Bei,
Jiang Qian,
Li Wenxin,
Li Zhaoshen
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1023.4
Subject(s) - medicine , inflammatory bowel disease , colitis , estrogen receptor , receptor , therapeutic effect , visceral pain , exacerbation , inflammation , estrogen receptor beta , endocrinology , gastroenterology , disease , nociception , cancer , breast cancer
IBD is an inflammatory condition of the bowel system, represented by cumulating and recurring abdominal pain, diarrhea and bloody stools. ERβ has been shown to play a therapeutic role in IBD, while P2X3 receptor (P2X3R) and P2X7 receptor (P2X7R) have been known to promote the initiation and exacerbation of IBD. However, the mechanism how ERβ exerts therapeutic effects and its relationship with P2X3R and P2X7R in IBD are still unknown. In our study, animal behavior tests, histological staining, western blotting, ELISA, and visceromotor reflex recording were used to determine whether the therapeutic effect of ERβ in IBD was through down‐regulation of the expression and function of P2X3R and P2X7R. Based on the successful model of IBD characterized by more weight loss, higher DAI scores and significant inflammatory responses, the expressions of P2X3, P2X7 and ERβ in different tissues including rectocolon, dorsal root ganglia (DRG) and dorsal horn of spinal cord (SCDH) were examined. We found that in colitis group, the expressions of ERβ in rectocolon, DRG and SCDH were all significantly reduced, while that of P2X3R were significantly increased in rectocolon and DRG, but not SCDH, and P2X7R was significantly increased only in rectocolon, but not DRG and SCDH, compared with control group. After administration of A317491 or BBG, antagonists of P2X3R and P2X7R, the weight loss, DAI scores and inflammatory responses of colitis rats in antagonists‐treated groups were all significantly reversed compared with those of control group. Likewise, when agonists of ERβ, DPN and ERB‐041 were given, there was also such a therapeutic role, and at the same time, so did ERβ transfection with recombinant lentivirus. As to the expressions of P2X3R and P2X7R, DPN could significantly decreased P2X3R in all the three fields, namely rectocolon, DRG and SCDH, while P2X7R was decreased only in rectocolon. However, ERB‐041 could decrease P2X3R and P2X7R both in rectocolon only, but not DRG. Furthermore, DPN inhibited visceromotor reflex by colonic extension and secretion of proinflammatory factors, IL‐1b, TNF‐a and IL‐6, in colitis rats. In brief, these results suggest that ERβ may play an important therapeutic role in IBD through down‐regulation of P2X3R and P2X7R. Therefore, it will provide certain evidences and new therapeutic strategies for clinical treatment towards IBD. Support or Funding Information This study is supported by National Natural Science Foundation of China (No, 31471103).