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Major histocompatibility complex class I–related chains A and B (MIC A/B): A novel role in nonalcoholic steatohepatitis
Author(s) -
Kahraman Alisan,
Schlattjan Martin,
Kocabayoglu Peri,
YildizMeziletoglu Sule,
Schlensak Matthias,
Fingas Christian D.,
Wedemeyer Inga,
Marquitan Guido,
Gieseler Robert K.,
Baba Hideo A.,
Gerken Guido,
Canbay Ali
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23253
Subject(s) - tunel assay , biology , terminal deoxynucleotidyl transferase , steatohepatitis , fibrosis , pathology , microbiology and biotechnology , medicine , immunology , endocrinology , fatty liver , immunohistochemistry , disease
Stress‐induced soluble major histocompatibility complex class I–related chains A/B (MIC A/B) are increased in chronic liver diseases and hepatocellular malignancy. We investigated the impact of these molecules on liver injury, apoptosis, and fibrosis in nonalcoholic steatohepatitis (NASH). Blood and liver tissue were obtained from 40 patients with NASH undergoing bariatric surgery for obesity. The control group consisted of 10 healthy individuals. We also investigated 10 patients with nonalcoholic fatty liver (NAFL). Polymerase chain reaction was used to measure messenger RNA (mRNA) transcripts of MIC A/B, natural killer cell receptor G2D (NKG2D), CD95/Fas, and tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL)–death receptor 5 (DR5). Apoptosis was quantified by way of terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL) (intrahepatic) and M30/M65 (systemic). Liver injury was assessed histopathologically and serologically (alanine aminotransferase/aspartate aminotransferase). Fibrosis was identified by Sirius red staining, quantitative morphometry, and α‐smooth muscle actin and collagen 1α transcripts. Compared with controls, patients with NASH revealed significant increases in (1) NKG2D mRNA (13.1‐fold) and MIC A/B mRNA (3.6‐fold and 15.8‐fold, respectively); (2) TRAIL–DR5 and CD95/Fas mRNA (2.7‐fold and 3.6‐fold, respectively); (3) TUNEL‐positive hepatocytes (4.0‐fold); and (4) M30 and M65 levels (4.6‐fold and 3.4‐fold, respectively). We found relevant correlations between MIC protein expression rates and NAS and fibrosis stages. In contrast, NKG2D and MIC A/B transcripts were attenuated in patients with NAFL compared with NASH. Histopathologically, NASH patients revealed increased NAS scores, an accumulation of natural killer cells, and 2.7‐fold increased hepatic fibrosis by quantitative morphometry. Conclusion: Our findings suggest an important role for MIC A/B in liver injury. Therapeutic intervention aimed at reducing MIC A/B levels may beneficially affect the progression of NASH. (H EPATOLOGY 2009.)