Abstract | BACKGROUND & AIMS: METHODS: We exposed esophageal squamous and Barrett's epithelial cells to LPS and measured the following: (1) TLR4, pro-IL1β, pro-IL18, and NLRP3 expression; (2) caspase-1 activity; (3) tumor necrosis factor-α, IL8, IL1β, and IL18 secretion; (4) lactate dehydrogenase (LDH) release (a pyroptosis marker); and (5) mitochondrial reactive oxygen species (ROS). As inhibitors, we used acetyl-Tyr-Val-Ala-Asp-CHO for caspase-1, small interfering RNA for NLRP3, and (2-(2,2,6,6,-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride for mitochondrial ROS. RESULTS: Squamous and Barrett's cells expressed similar levels of TLR4, but LPS induced TLR4 signaling that increased tumor necrosis factor-α and IL8 secretion only in Barrett's cells. Barrett's cells treated with LPS showed increased expression of pro-IL18, pro-IL1β, and NLRP3, and increased mitochondrial ROS levels, caspase-1 activity, IL1β and IL18 secretion, and LDH release. Acetyl-Tyr-Val-Ala-Asp-CHO, NLRP3 small interfering RNA, and Mito- TEMPO all blocked LPS-induced IL1β and IL18 secretion and LDH release. CONCLUSIONS:
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Authors | Yuji Nadatani, Xiaofang Huo, Xi Zhang, Chunhua Yu, Edaire Cheng, Qiuyang Zhang, Kerry B Dunbar, Arianne Theiss, Thai H Pham, David H Wang, Toshio Watanabe, Yasuhiro Fujiwara, Tetsuo Arakawa, Stuart J Spechler, Rhonda F Souza |
Journal | Cellular and molecular gastroenterology and hepatology
(Cell Mol Gastroenterol Hepatol)
Vol. 2
Issue 4
Pg. 439-453
(Jul 2016)
ISSN: 2352-345X [Print] United States |
PMID | 27777967
(Publication Type: Journal Article)
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