Adaptive cytoprotection against deoxycholate-induced injury in human gastric cells in vitro -: Is there a role for endogenous prostaglandins?

被引:23
作者
Kokoska, ER [1 ]
Smith, GS [1 ]
Rieckenberg, CL [1 ]
Deshpande, Y [1 ]
Banan, A [1 ]
Miller, TA [1 ]
机构
[1] St Louis Univ, Hlth Sci Ctr, Dept Surg, Theodore Cooper Surg Res Inst, St Louis, MO 63104 USA
关键词
adaptive cytoprotection; prostaglandins; bile salts; AGS cells;
D O I
10.1023/A:1018826416864
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The majority of previous work investigating adaptive cytoprotection has involved in vivo studies, which have suggested that this protective response is in large part mediated by endogenous prostaglandins (PGs). The aim of this study was to investigate adaptive cytoprotection under in vitro conditions in human gastric cells and to better delineate the role of endogenous PGs in this protective response. AGS cells (a human gastric carcinoma cell line) were characterized morphologically and subsequently used for all experiments. Sodium deoxycholate was used as both the mild irritant and the damaging agent, and cell injury was quantified using both a commercial viability/cytotoxicity kit as well as transepithelial permeability studies. Finally, endogenous PG synthesis in response to varying concentrations of deoxycholate was determined. AGS cells were determined to be morphologically similar to gastric mucous cells. Pretreatment of cells with low-dose deoxycholate significantly attenuated injury upon subsequent exposure tn damaging concentrations nf deoxycholate, and this protection was determined to be dependent upon both concentration and duration of mild irritant exposure. Preincubation of AGS cells with indomethacin reversed protection induced by mild irritant pretreatment and also significantly increased cellular susceptibility to injury. Results of the permeability studies closely paralleled those assessing cell mortality, While deoxycholate exposure increased PG synthesis, the concentrations required were much higher than those needed to initiate protection. Adaptive cytoprotection exists in AGS cells under in vitro conditions independent of intact blood flow, neural innervation, or circulating humoral mediators. While this protection is reversed by indomethacin, it appears that this reversal results from increased cellular injury secondary to diminished basal PGs? rather than inhibition of endogenous PG synthesis.
引用
收藏
页码:806 / 815
页数:10
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