Upregulated mRNA expression of major histocompatibility complex class I chain-related gene A in colon and activated natural killer cells of Chinese patients with ulcerative colitis

J Dig Dis. 2011 Apr;12(2):82-9. doi: 10.1111/j.1751-2980.2010.00464.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism*
  • Colon / metabolism*
  • Female
  • Flow Cytometry
  • Gene Expression
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Killer Cells, Natural / metabolism*
  • Male
  • Middle Aged
  • NK Cell Lectin-Like Receptor Subfamily K / immunology*
  • Peptide Fragments / metabolism
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Young Adult

Substances

  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • MHC class I-related chain A
  • MICB antigen
  • NK Cell Lectin-Like Receptor Subfamily K
  • Peptide Fragments
  • RNA, Messenger
  • interferon gamma (1-39)
  • Interferon-gamma