[Role of p38 mitogen-activated protein kinase pathway in pathogenesis of ulcerative colitis].

Abstract

OBJECTIVE:

To elucidate the role of p38 mitogen-activated protein kinase (p38MAPK) in the pathogenesis of ulcerative colitis (UC) and DSS-induced colitis in mice.

METHODS:

(1) 27 Balb/c mice were divided randomly into three groups: DSS-induced colitis group, normal control group and SB203580 treatment group. In DSS-induced colitis group, mice were feed with 5% DSS solution. In SB203580 treatment group, mice were feed with 5%DSS solution for 72 hours, then treated with intraperitoneal injection of SB203580 (1 mg/kg) once daily. Disease activity index (DAI) was record to evaluate the severity of colitis. The mice were executed after 7 days. The levels of TNF-alpha and IL-1beta were measured by ELISA. (2) A total of 54 cases were included in the study. 36 cases were patients with active ulcerative colitis, 18 cases were normal mucosa from 18 colon cancer cases served as control. Effects of SB203580 (a selective p38MAPK inhibitor) on expression of TNF-alpha and IL-1beta in intestinal mucosal biopsy specimens from patients with ulcerative colitis were determined on condition of tissue culture.

RESULTS:

(1) The DAI scores, the levels of TNF-alpha and IL-1beta in SB203580 group were lower significantly compared with DSS group (P < 0.05), and were increased significantly compared with normal control group (P < 0.05). (2) The levels of TNF-alpha and IL-1beta in intestinal mucosal biopsy specimens in SB203580 treatment group were lower significantly than those in UC group (P < 0.05).

CONCLUSION:

SB203580 can inhibit p38MAPK signal transduction pathway, then reduce the expression of pro-inflammatory cytokine TNF-alpha and IL-1beta.

• Authors: Fu-Qian He, Yu-Pei Zou, Xiao-Li Huang, Feng-Jiao Gao, Lan Peng, Hua-Tian Gan
• Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition (Sichuan Da Xue Xue Bao Yi Xue Ban) Vol. 44 Issue 3 Pg. 393-6, 401 (May 2013) ISSN: 1672-173X [Print] China
• PMID: 23898520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Imidazoles
• Interleukin-1beta
• Pyridines
• Tumor Necrosis Factor-alpha
• Dextran Sulfate
• p38 Mitogen-Activated Protein Kinases
• SB 203580

Topics

• Animals
• Colitis, Ulcerative (chemically induced, etiology, physiopathology)
• Dextran Sulfate
• Female
• Imidazoles (pharmacology)
• Interleukin-1beta (metabolism)
• Intestinal Mucosa (metabolism)
• MAP Kinase Signaling System (physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Pyridines (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)