title: HMGB1/RAGE induces IL-17 expression to exaggerate inflammation in peripheral blood cells of hepatitis B patients.
abstract: BACKGROUND
  Hepatitis B (HB) is an infectious disease with unfavorable consequence for patients and involved in chronic inflammation of liver. The present study aimed to investigate whether High-mobility group protein B (HMGB)1/receptor for advanced glycation end products (RAGE) aggravates inflammation enhancing the expression of interleukin (IL)-17.
  
  
  METHODS
  Mild and severe HB liver tissue and peripheral blood samples were obtained intra-operatively. Histological analysis of the livers was performed by immunohistochemistry. IL-1β and IL-6 of liver tissue were detected by confocal microscopy staining. Relative mRNA expression was measured by real-time PCR and protein levels were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  HMGB1, RAGE and IL-17 expression is increased in liver of HB patients with acute on chronic liver failure (ACLF) compared to healthy controls. HMGB1 treatment induced inflammatory cytokines including IL-17 in peripheral blood cells of HB patients. IL-17 also induced the expression of RAGE and IL-1β in peripheral blood cells of HB patients with ACLF. On the other hands, the inhibitory factor of p38 and nuclear factor-kappa B reduced the expression of RAGE and IL-1β in peripheral blood cells HB patients with ACLF.
  
  
  CONCLUSIONS
  HMGB1, RAGE and IL-17 expression is increased in liver of severe HB patients. HMGB1 and RAGE interaction may contribute to the inflammation of liver enhancing the expression of IL-17, which can be possibly restored through the decline of the HMGB1/RAGE axis.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. jhunjy@catholic.ac.kr.
authors.forename: JooYeon
authors.initials: J
authors.lastname: Jhun
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. redcap817@catholic.ac.kr.
authors.forename: SeungHoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea. hee82@catholic.ac.kr.
authors.forename: HeeYeon
authors.initials: H
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. yangmi@catholic.ac.kr.
authors.forename: Yang-Mi
authors.initials: YM
authors.lastname: Her
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. jkbyun0228@catholic.ac.kr.
authors.forename: Jae Kyeong
authors.initials: JK
authors.lastname: Byun
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. mnikek@catholic.ac.kr.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea. blackiqq@gmail.com.
authors.forename: Soon Kyu
authors.initials: SK
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea. iammila@catholic.ac.kr.|Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea. iammila@catholic.ac.kr.|Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea. iammila@catholic.ac.kr.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea. jychoi@catholic.ac.kr.
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000378:metabolism*; D006509:Hepatitis B / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C000593871:AGER protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D048051:p38 Mitogen-Activated Protein Kinases