| First Author | Shao BZ | Year | 2019 |
| Journal | Inflammation | Volume | 42 |
| Issue | 5 | Pages | 1666-1679 |
| PubMed ID | 31236857 | Mgi Jnum | J:294483 |
| Mgi Id | MGI:6456475 | Doi | 10.1007/s10753-019-01027-9 |
| Citation | Shao BZ, et al. (2019) Alpha7 Nicotinic Acetylcholine Receptor Alleviates Inflammatory Bowel Disease Through Induction of AMPK-mTOR-p70S6K-Mediated Autophagy. Inflammation 42(5):1666-1679 |
| abstractText | Alpha7 nicotinic acetylcholine receptor (alpha7nAChR) has been reported to be protective in several kinds of disorders through inflammatory suppression. Here, we investigated the role of alpha7nAChR in inflammatory bowel disease (IBD) on alpha7nAChR deficient mice (alpha7nAChR(-/-)) and the wild-type mice (alpha7nAChR(+/+)). Three percent dextran sulfate sodium (DSS) was used for the creation of IBD mice model and lipopolysaccharides (LPS)/DSS as an inflammatory stressor in murine bone marrow-derived macrophages (BMDMs). The severity of IBD was determined and HE staining as well as enzyme-linked immunosorbent assay (ELISA) and real-time PCR were used to detect the level of inflammatory activation. Western blot was used to determine the levels of autophagy-related proteins. Transmission electron microscopy and mRFP-GFP-LC3 plasmid were applied to determine the levels of autophagy. We demonstrated that deficiency in alpha7nAChR produced a detrimental effect on IBD severity and inflammatory reaction in DSS-induced colitis models. Those effects were led to via autophagy dysfunction. alpha7nAChR deficiency attenuated the protective and anti-inflammatory effect of autophagy inducer in IBD mice and BMDMs challenged with LPS/DSS. The alleviative effect of activating alpha7nAChR was attenuated through inhibiting adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated signaling. In conclusion, alpha7nAChR contributes to alleviate IBD through the induction of AMPK-mammalian target of rapamycin rabbit (mTOR)-p70 ribosomal protein S6 kinase (p70S6K)-mediated autophagy, thus providing a novel target for the treatment of IBD. |
