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Objective: To explore the expression of major histocompatibility complex class I chain-related gene A (MICA) and its ligand in colonic mucosa and the role of MICA-natural killer (NK) group 2D (NKG2D) interaction in activating NK cells in ulcerative colitis (UC) patients., Methods: Intestinal mucosal biopsies were obtained from patients with UC and the controls. The expression of major histocompatibility complex class I-related gene (MIC) genes was determined by a reverse transcription polymerase chain reaction (RT-PCR) and the imaging of MICA expressed on colonic mucosa was measured by confocal microscopy resonance scanning. NKG2D and intracellular interferon (IFN)-γ expressions on NK cells were assayed by flow cytometry., Results: The relative amount of MICA mRNA in the colonic mucosa of UC patients was significantly higher than in that of the controls (3.5408 ± 2.6658 vs 1.0477 ± 0.7201, P = 0.001), as were the major histocompatibility complex class I chain-related gene B (MICB) (8.9879 ± 3.2893 vs 4.6293 ± 1.2616, P < 0.001) and NKG2D mRNA expression (2.4395 ± 0.8147 vs 1.1624 ± 0.3954, P < 0.001). Confocal microscopy resonance scanning had shown that MICA was localized predominantly on the basolateral membranes of the epithelium. Further flow cytometry confirmed that the percentage of IFN-γ producer NK cells that expressed NKG2D in peripheral blood lymphocytes was higher in UC patients than in the healthy controls (45.36% ± 12.47% vs 27.45% ± 9.30%, P < 0.001)., Conclusion: MICA, MICB and NKG2D were upregulated in the colonic mucosa of UC and were associated with activating NK cells with promoted NKG2D and IFN-γ production., (© 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

Objective: Our aim was to investigate the expression of cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) in ulcerative colitis (UC) and to evaluate the effect of CTLA-4 gene -1661A/G polymorphism on CTLA-4 expression and transcription., Methods: A total of 20 UC patients and 22 healthy controls matched by age and sex were enrolled at Zhongnan Hospital of Wuhan University in central China. The CTLA-4 -1661A/G polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. A Western blot analysis was performed to determine the full length CTLA-4 (flCTLA-4) protein expression in the peripheral blood of the UC patients. Serum-soluble CTLA-4 (sCTLA-4) levels were measured by enzyme-linked immunosorbent assay. CTLA-4-1661G mutant promoter transcription function was analyzed by site-directed PCR-based mutagenesis., Results: CTLA-4 protein expression on CD4(+) T cells in UC patients was lower than that in the healthy controls (P < 0.001) while serum sCTLA-4 in the UC patients was significantly higher than that in the healthy controls (P < 0.001). No correlation was found between flCTLA-4 and sCTLA-4 expression levels and the -1661 A/G polymorphism of the CTLA-4 gene. Meanwhile, CTLA-4 -1661 allele A had no significant impact on the promoter activity compared with allele G (P > 0.05)., Conclusion: CTLA-4 expressions were aberrant in UC patients compared with the healthy controls. CTLA-4 -1661A/G polymorphism had no significant impact on CTLA-4 expression and transcription in the peripheral CD4 T cells of UC patients., (© 2010 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)