title: Major histocompatibility complex class I-related chains A and B (MIC A/B): a novel role in nonalcoholic steatohepatitis.
abstract: 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 alpha-smooth muscle actin and collagen 1alpha 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, University Hospital Essen, Germany.
authors.forename: Alisan
authors.initials: A
authors.lastname: Kahraman
authors.forename: Martin
authors.initials: M
authors.lastname: Schlattjan
authors.forename: Peri
authors.initials: P
authors.lastname: Kocabayoglu
authors.forename: Sule
authors.initials: S
authors.lastname: Yildiz-Meziletoglu
authors.forename: Matthias
authors.initials: M
authors.lastname: Schlensak
authors.forename: Christian D
authors.initials: CD
authors.lastname: Fingas
authors.forename: Inga
authors.initials: I
authors.lastname: Wedemeyer
authors.forename: Guido
authors.initials: G
authors.lastname: Marquitan
authors.forename: Robert K
authors.initials: RK
authors.lastname: Gieseler
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D000328:Adult; D017209:Apoptosis; D005234:Fatty Liver / Q000276:immunology / Q000473:pathology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis
chemical_list: D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand