[Effects of PI3K signaling pathway on pathogenesis of ulcerative colitis].
OBJECTIVE
To elucidate the role of PI3K/Akt in the pathogenesis of UC patients and DSS-induced colitis model in mice.


METHODS
(1) The mucosa biopsy specimens were collected from 40 patients with ulcerative colitis, and normal mucosa from 20 colon cancer cases served as control. Effects of wortmannin on expression of TNF-alpha in intestinal mucosal specimens from patients with ulcerative colitis were determined on the condition of tissue culture. (2) Thirty six Balb/c mice were divided randomly into four groups: normal control group, DSS-induced colitis group, DMSO control group and wortmannin treatment group. Colitis was induced by feeding 5% DSS in mice. Disease activity index (DAI) was evaluated and the level of TNF-alpha was measured by ELISA.


RESULTS
(1) The TNF-alpha level of intestinal mucosa in wortmannin treatment group was significantly lower than that in UC group (P < 0.05). (2) The DAI scores and TNF-alpha levels were lower significantly in wortmannin treatment group compared with DSS group and DMSO group (P < 0.05), and were higher than those of normal control group (P < 0.05). There were no significance between DSS group and DMSO group (P > 0.05).


CONCLUSIONS
PI3K/Akt signal transduction pathway participates in the expression regulation of pro-inflammatory cytokine TNF-alpha. Wortmannin can inhibit PI3K/Akt signal transduction pathway.
Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
Xiao-Li
XL
Huang
Yu-Xia
YX
Zheng
Zai-Bo
ZB
Liao
Jing
J
Yin
Hua-Tian
HT
Gan
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000077191:Wortmannin
D000730:Androstadienes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D000077191:Wortmannin