본문 바로가기
KERD
논문KCI 등재

Involvement of Hepatic Innate Immunity in Alcoholic Liver Disease

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/ NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.

Abstract

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/ NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.

참고문헌 (65)

  1. Williams R, "Global challenges in liver disease", Hepatology, 44, pp.521~526 (2006)
  2. O’Shea RS, "Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology: Alcoholic liver disease", Hepatology, 51, pp.307~328 (2010)
  3. Jeong WI, "Innate immunity and alcoholic liver fibrosis", J Gastroenterol Hepatol, 23(1), pp.S112~S118 (2008)
  4. Purohit V, "Molecular mechanisms of alcoholic fatty liver", Alcohol Clin Exp Res, 33, pp.191~205 (2009)
  5. Purohit V, "Mechanisms of alcohol-induced hepatic fibrosis: a summary of the Ron Thurman Symposium", Hepatology, 43, pp.872~878 (2006)
  6. Gao B, "Liver: An organ with predominant innate immunity", Hepatology, 47, pp.729~736 (2008)
  7. Racanelli V, "The liver as an immunological organ", Hepatology, 43(2 Suppl 1), pp.S54~S62 (2006)
  8. Crispe IN, "The liver as a lymphoid organ", Annu Rev Immunol, 27, pp.147~163 (2009)
  9. Doherty DG, "Innate and adaptive lymphoid cells in the human liver", Immunol Rev, 174, pp.5~20 (2000)
  10. Jeong WI, "Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver", Cell Metab, 7, pp.227~235 (2008)
  11. Jeong WI, "Abrogation of the antifibrotic effects of natural killer cells", interferon-gamma contributes to alcohol acceleration of liver fibrosis, 2008, pp.134, 248~258
  12. Mandrekar P, "Signalling pathways in alcohol-induced liver inflammation", J Hepatol, 50, pp.1258~1266 (2009)
  13. Otani K, "Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells", Gastroenterology, 128, pp.96~107 (2005)
  14. Lieber CS, "Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis", Alcohol, 34, pp.9~19 (2004)
  15. Crabb DW, "Recent developments in alcoholism: the liver", Recent Dev Alcohol, 11, pp.207~230 (1993)
  16. Fromenty B, "Microvesicular steatosis and steatohepatitis: role of mitochondrial dysfunction and lipid peroxidation", J Hepatol, 26(Suppl 1), pp.13~22 (1997)
  17. Yahagi N, "Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)", Lep(ob) mice, 2002, pp.277, 19353~19357
  18. You M, "The role of AMP-activated protein kinase in the action of ethanol in the liver", Gastroenterology, 127, pp.1798~1808 (2004)
  19. Costet P, "Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis", J Biol Chem, 273, pp.29577~29585 (1998)
  20. Ip E, "Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice", Hepatology, 38, pp.123~132 (2003)
  21. Nagy LE, "Recent insights into the role of the innate immune system in the development of alcoholic liver disease", Exp Biol Med, 228, pp.882~890 (2003)
  22. Bird GL, "Increased plasma tumor necrosis factor in severe alcoholic hepatitis", Ann Intern Med, 112, pp.917~920 (1990)
  23. Lin HZ, "Chronic ethanol consumption induces the production of tumor necrosis factor-alpha and related cytokines in liver and adipose tissue", Alcohol Clin Exp Res, 22(5 Suppl), pp.231S~237S (1998)
  24. Pritchard MT, "Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice", Gastroenterology, 132, pp.1117~1126 (2007)
  25. Ji C, "Role of TNF-alpha in ethanol-induced hyperhomocysteinemia and murine alcoholic liver injury", Hepatology, 40, pp.442~451 (2004)
  26. Yin M, "Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice", Gastroenterology, 117, pp.942~952 (1999)
  27. Lawler JF Jr, "Tumor necrosis factor-alpha stimulates the maturation of sterol regulatory element binding protein-1 in human hepatocytes through the action of neutral sphingomyelinase", J Biol Chem, 273, pp.5053~5059 (1998)
  28. Endo M, "TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c)", Exp Biol Med, 232, pp.614~621 (2007)
  29. Kang L, "Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines", Alcohol Clin Exp Res, 31, pp.1581~1588 (2007)
  30. El-Assal O, "IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver", Cell Mol Immunol, 1, pp.205~211 (2004)
  31. Hong F, "Interleukin 6 alleviates hepatic steatosis and ischemia", re perfusion injury in mice with fatty liver disease, 2004, pp.40, 933~941
  32. Horiguchi N, "Cell type-dependent pro- and anti-inflammatory role of signal transducer and activator of transcription 3 in alcoholic liver injury", Gastroenterology, 134, pp.1148~1158 (2008)
  33. Radaeva S, "Retinoic acid signaling sensitizes hepatic stellate cells to NK cell killing via upregulation of NK cell activating ligand RAE1", Am J Physiol Gastrointest Liver Physiol, 293, pp.G809~G816 (2007)
  34. Jeong WI, "STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity", Hepatology, 44, pp.1441~1451 (2006)
  35. Radaeva S, "Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners", Gastroenterology, 130, pp.435~452 (2006)
  36. McClain CJ, "Cytokines in alcoholic liver disease", Semin Liver Dis, 19, pp.205~219 (1999)
  37. Szabo G, "Consequences of alcohol consumption on host defence", Alcohol Alcohol, 34, pp.830~841 (1999)
  38. Akira S, "Pathogen recognition and innate immunity", Cell, 124, pp.783~801 (2006)
  39. Seki E, "Toll-like receptors and adaptor molecules in liver disease: update", Hepatology, 48, pp.322~335 (2008)
  40. Uesugi T, "Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice", Hepatology, 34, pp.101~108 (2001)
  41. Chow JC, "Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction", J Biol Chem, 274, pp.10689~10692 (1999)
  42. Visintin A, "Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4", Proc Natl Acad Sci USA, 98, pp.12156~12161 (2001)
  43. Wright SD, "Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages", J Exp Med, 170, pp.1231~1241 (1989)
  44. Uesugi T, "Role of lipopolysaccharide-binding protein in early alcohol-induced liver injury in mice", J Immunol, 168, pp.2963~2969 (2002)
  45. Yin M, "Reduced early alcohol-induced liver injury in CD14-deficient mice", J Immunol, 166, pp.4737~4742 (2001)
  46. Nanji AA, "Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease)", Proc Soc Exp Biol Med, 205, pp.243~247 (1994)
  47. Kawai T, "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors", Nat Immunol, 11, pp.373~384 (2010)
  48. Hritz I, "The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88", Hepatology, 48, pp.1224~1231 (2008)
  49. Bautista AP, "Neutrophilic infiltration in alcoholic hepatitis", Alcohol, 27, pp.17~21 (2002)
  50. Kono H, "NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease", J Clin Invest, 106, pp.867~872 (2000)
  51. Thakur V, "Chronic ethanol feeding increases activation of NADPH oxidase by lipopolysaccharide in rat Kupffer cells: role of increased reactive oxygen in LPS-stimulated ERK1", 2 activation and TNF-alpha production, 2006, pp.79, 1348~1356
  52. Wheeler MD, "Delivery of the Cu", Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats, 2001, pp.120, 1241~1250
  53. "High glucose induces toll-like receptor expression in human monocytes: mechanism of activation", Diabetes, 57, pp.90~3098 (2008)
  54. Park HS, "Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B", J Immunol, 173, pp.3589~3593 (2004)
  55. Friedman SL, "Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver", Physiol Rev, 88, pp.125~172 (2008)
  56. Melhem A, "Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC", J Hepatol, 45, pp.60~71 (2006)
  57. Taimr P, "Activated stellate cells express the TRAIL receptor-2", death receptor-5 and undergo TRAIL-mediated apoptosis, 2003, pp.37, 87~95
  58. Baroni GS, "Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis", Hepatology, 23, pp.1189~1199 (1996)
  59. Park O, "Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride", Hepatology, 49, pp.1683~1694 (2009)
  60. Laso FJ, "Decreased natural killer cytotoxic activity in chronic alcoholism is associated with alcohol liver disease but not active ethanol consumption", Hepatology, 25, pp.1096~1100 (1997)
  61. Pan HN, "Chronic ethanol consumption inhibits hepatic natural killer cell activity and accelerates murine cytomegalovirus-induced hepatitis", Alcohol Clin Exp Res, 30, pp.1615~1623 (2006)
  62. Szabo G, "A recent perspective on alcohol, immunity, and host defense", Alcohol Clin Exp Res, 33, pp.220~232 (2009)
  63. Szabo G, "Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and transforming growth factor-beta production", Alcohol Clin Exp Res, 20, pp.900~907 (1996)
  64. Jaruga B, "Chronic alcohol consumption accelerates liver injury in T cell-mediated hepatitis: alcohol disregulation of NF-kappaB and STAT3 signaling pathways", Am J Physiol Gastrointest Liver Physiol, 287, pp.G471~G479 (2004)
  65. Minagawa M, "Activated natural killer T cells induce liver injury by Fas and tumor necrosis factor-alpha during alcohol consumption", Gastroenterology, 126, pp.1387~1399 (2004)

관련 논문AI추천

이 간행물의 다른 논문 (8건)