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Cited by 392Alcohol Consumption and Health EffectsLiver physiology and pathologyLiver Disease Diagnosis and Treatment

Inflammatory pathways in alcoholic steatohepatitis

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Gao, Bin, Ahmad, Maleeha F., Nagy, Laura E., Tsukamoto, Hidekazu·2019·Journal of Hepatology
DOI 10.1016/j.jhep.2018.10.023PMC PMC6361545
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Abstract

Inflammatory processes are primary contributors to the development and progression of alcoholic steatohepatitis (ASH), with severe alcoholic hepatitis characterised by non-resolving inflammation. Inflammation in the progression of ASH is a complex response to microbial dysbiosis, loss of barrier integrity in the intestine, hepatocellular stress and death, as well as inter-organ crosstalk. Herein, we review the roles of multiple cell types that are involved in inflammation in ASH, including resident macrophages and infiltrating monocytes, as well as other cell types in the innate and adaptive immune system. In response to chronic, heavy alcohol exposure, hepatocytes themselves also contribute to the inflammatory process; hepatocytes express a large number of chemokines and inflammatory mediators and can also release damage-associated molecular patterns during injury and death. These cellular responses are mediated and accompanied by changes in the expression of pro- and anti-inflammatory cytokines and chemokines, as well as by signals which orchestrate the recruitment of immune cells and activation of the inflammatory process. Additional mechanisms for cell-cell and inter-organ communication in ASH are also reviewed, including the roles of extracellular vesicles and microRNAs, as well as inter-organ crosstalk. We highlight the concept that inflammation also plays an important role in promoting liver repair and controlling bacterial infection. Understanding the complex regulatory processes that are disrupted during the progression of ASH will likely lead to better targeted strategies for therapeutic interventions.

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  • Levels of pro-inflammatory cytokines TNFα, IL-1β, and IL-8 are upregulated in patients with ALD.

    “The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, and IL-8, are upregulated in patients with ALD [70].”

    From Pathophysiological Aspects of Alcohol Metabolism in the Liver (2021) · cites this paper as [70]

    The “Cytokines and chemokines” section reports that many cytokines are highly upregulated in liver and serum from patients with severe alcoholic hepatitis, and the “Hepatocytes” section specifically reports elevated IL-8 in those patients. It says cytokines are only probably elevated in mild and moderate ALD, so it does not establish the claim without that severity qualifier. It also classifies IL-8 as a chemokine rather than a cytokine. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Gut dysbiosis and increased intestinal permeability are frequently features of both MASH and ASH.

    “Gut dysbiosis and increased intestinal permeability is frequently a feature of both diseases(212, 213), while LPS-mediated activation of KCs via TLR4 leading to MyD88-dependent activation of NF-kB, production of proinflammatory cytokines”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [213]

    The section “Pathways to inflammation in ASH—Loss of intestinal integrity and dysbiosis” (page unavailable) identifies gut dysbiosis and impaired intestinal barrier function as contributors to ASH and says chronic alcohol consumption increases gut permeability. The passages do not address whether these are frequent features of MASH, so the claim about both diseases is not fully supported by this source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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  1. [1]Thurman RG II.. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol 1998; 275: G605– 11. 9756487
  2. [2]Wang M, You Q, Lor K, Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice. J Leukoc Biol 2014; 96: 657– 65. 25030420 PMC4163632
  3. [3]Ju C, Mandrekar P. Macrophages and Alcohol-Related Liver Inflammation. Alcohol Res 2015; 37: 251– 62. 26717583 PMC4590621
  4. [4]Nagy LE. The Role of Innate Immunity in Alcoholic Liver Disease. Alcohol Res 2015; 37: 237– 50. 26695748 PMC4590620
  5. [5]Xu J, Chi F, Guo T, NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation. J Clin Invest 2015; 125: 1579– 90. 25798621 PMC4396469
  6. [7]Ramachandran P, Pellicoro A, Vernon MA, Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A 2012; 109: E3186– 95. 23100531 PMC3503234
  7. [8]Wang M, Frasch SC, Li G, Role of gp91(phox) in hepatic macrophage programming and alcoholic liver disease. Hepatol Commun 2017; 1: 765– 779. 29404493 PMC5678917
  8. [9]Wang J, Kubes P. A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair. Cell 2016; 165: 668– 78. 27062926
  9. [10]Bertola A, Park O, Gao B. Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury: A critical role for E-selectin. Hepatology 2013. PMC3726575 23532958
  10. [11]Li M, He Y, Zhou Z, MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6- p47(phox)-oxidative stress pathway in neutrophils. Gut 2017; 66: 705– 715. 27679493 PMC5458746
  11. [12]Lazaro R, Wu R, Lee S, Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice. Hepatology 2015; 61: 129– 40. 25132354 PMC4280361
  12. [13]Altamirano J, Miquel R, Katoonizadeh A, A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014; 146: 1231– 9 e1–6. 24440674 PMC3992184
  13. [14]Rajkovic IA, Williams R. Abnormalities of neutrophil phagocytosis, intracellular killing and metabolic activity in alcoholic cirrhosis and hepatitis. Hepatology 1986; 6: 252– 62. 3007318
  14. [15]Singh V, Sharma AK, Narasimhan RL, Granulocyte colony-stimulating factor in severe alcoholic hepatitis: a randomized pilot study. Am J Gastroenterol 2014; 109: 1417– 23. 24935272
  15. [16]Chedid A, Mendenhall CL, Moritz TE, Cell-mediated hepatic injury in alcoholic liver disease. Veterans Affairs Cooperative Study Group 275. Gastroenterology 1993; 105: 254– 66. 8514042
  16. [17]Li W, Amet T, Xing Y, Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study. Hepatology 2017; 66: 575– 590. 28466561 PMC5548491
  17. [18]Liaskou E, Klemsdal Henriksen EK, Holm K, High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires. Hepatology 2016; 63: 1608– 19. 26257205
  18. [19]Markwick LJ, Riva A, Ryan JM, Blockade of PD1 and TIM3 restores innate and adaptive immunity in patients with acute alcoholic hepatitis. Gastroenterology 2015; 148: 590– 602 e10. 25479137
  19. [20]Sutti S, Bruzzi S, Albano E. The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: a 2015 update. Expert Rev Gastroenterol Hepatol 2016; 10: 243– 53. 26634783
  20. [21]Lin F, Taylor NJ, Su H, Alcohol dehydrogenase-specific T-cell responses are associated with alcohol consumption in patients with alcohol-related cirrhosis. Hepatology 2013; 58: 314– 24. 23424168
  21. [23]Gao B, Xiang X. Interleukin-22 from bench to bedside: a promising drug for epithelial repair. Cell Mol Immunol 2018. PMC6804818 29921965
  22. [25]Gao Y, Zhou Z, Ren T, Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2- deficient mice and humans: roles of acetaldehyde and glucocorticoids. Gut 2018. PMC6582747 30121625
  23. [26]Mathews S, Feng D, Maricic I, Invariant natural killer T cells contribute to chronic-plus- binge ethanol-mediated liver injury by promoting hepatic neutrophil infiltration. Cell Mol Immunol 2016; 13: 206– 16. 25661730 PMC4786627
  24. [27]Cui K, Yan G, Xu C, Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin-1beta in mice. J Hepatol 2015; 62: 1311– 8. 25582105
  25. [28]Wong EB, Ndung’u T, Kasprowicz VO. The role of mucosal-associated invariant T cells in infectious diseases. Immunology 2017; 150: 45– 54. 27633333 PMC5341498
  26. [29]Riva A, Patel V, Kurioka A, Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease. Gut 2018; 67: 918– 930. 29097439 PMC5890654
  27. [30]Gao B, Ma J, Xiang X. MAIT cells: a novel therapeutic target for alcoholic liver disease? Gut 2018; 67: 784– 786. 29167178
  28. [31]Chang B, Xu MJ, Zhou Z, Short- or long-term high-fat diet feeding plus acute ethanol binge synergistically induce acute liver injury in mice: an important role for CXCL1. Hepatology 2015; 62: 1070– 85. 26033752 PMC4589443
  29. [32]Wang W, Xu MJ, Cai Y, Inflammation is independent of steatosis in a murine model of steatohepatitis. Hepatology 2017; 66: 108– 123. 28220523 PMC5481491
  30. [33]Ge X, Antoine DJ, Lu Y, High mobility group box-1 (HMGB1) participates in the pathogenesis of alcoholic liver disease (ALD). J Biol Chem 2014; 289: 22672– 91. 24928512 PMC4132775
  31. [34]Cai Y, Xu MJ, Koritzinsky EH, Mitochondrial DNA-enriched microparticles promote acute- on-chronic alcoholic neutrophilia and hepatotoxicity. JCI Insight 2017; 2. PMC5518559 28724791
  32. [35]Dominguez M, Miquel R, Colmenero J, Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis. Gastroenterology 2009; 136: 1639– 50. 19208360
  33. [36]Joshi-Barve S, Barve SS, Amancherla K, Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Hepatology 2007; 46: 823– 30. 17680645
  34. [37]Barnes MA, McMullen MR, Roychowdhury S, Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology 2013; 57: 1980– 91. 23174952 PMC3597752
  35. [39]Ambade A, Catalano D, Lim A, Inhibition of heat shock protein 90 alleviates steatosis and macrophage activation in murine alcoholic liver injury. J Hepatol 2014; 61: 903– 11. 24859453 PMC4169725
  36. [40]Xie J, Yang L, Tian L, Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury. Sci Rep 2016; 6: 27665. 27273604 PMC4897699
  37. [41]Hartmann P, Seebauer CT, Schnabl B. Alcoholic liver disease: the gut microbiome and liver cross talk. Alcohol Clin Exp Res 2015; 39: 763– 75. 25872593 PMC4402724
  38. [42]Rao R. Endotoxemia and gut barrier dysfunction in alcoholic liver disease. Hepatology 2009; 50: 638– 44. 19575462 PMC6209509
  39. [43]Banan A, Zhang LJ, Shaikh M, Novel effect of NF-kappaB activation: carbonylation and nitration injury to cytoskeleton and disruption of monolayer barrier in intestinal epithelium. Am J Physiol Cell Physiol 2004; 287: C1139– 51. 15175222
  40. [44]Cresci GA, Glueck B, McMullen MR, Prophylactic tributyrin treatment mitigates chronic- binge ethanol-induced intestinal barrier and liver injury. J Gastroenterol Hepatol 2017; 32: 1587– 1597. 28087985 PMC5511097
  41. [45]Tripathi A, Debelius J, Brenner DA, The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 2018; 15: 397– 411. 29748586 PMC6319369
  42. [46]Yang AM, Inamine T, Hochrath K, Intestinal fungi contribute to development of alcoholic liver disease. J Clin Invest 2017; 127: 2829– 2841. 28530644 PMC5490775
  43. [47]Ji C New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases. Int J Hepatol 2014; 2014: 513787. 24868470 PMC4020372
  44. [48]Wang S, Pacher P, De Lisle RC, A Mechanistic Review of Cell Death in Alcohol-Induced Liver Injury. Alcohol Clin Exp Res 2016; 40: 1215– 23. 27130888 PMC5455778
  45. [50]Lawlor KE, Khan N, Mildenhall A, RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun 2015; 6: 6282. 25693118 PMC4346630
  46. [51]Taabazuing CY, Okondo MC, Bachovchin DA. Pyroptosis and Apoptosis Pathways Engage in Bidirectional Crosstalk in Monocytes and Macrophages. Cell Chem Biol 2017; 24: 507– 514. e4. 28392147 PMC5467448
  47. [52]Wang Y, Gao W, Shi X, Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 2017; 547: 99– 103. 28459430
  48. [53]Kayagaki N, Stowe IB, Lee BL, Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 2015; 526: 666– 71. 26375259
  49. [54]Aglietti RA, Dueber EC. Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions. Trends Immunol 2017; 38: 261– 271. 28196749
  50. [55]Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 2010; 64: 163– 84. 20825345 PMC3525469
  51. [56]Kema VH, Mojerla NR, Khan I, Effect of alcohol on adipose tissue: a review on ethanol mediated adipose tissue injury. Adipocyte 2015; 4: 225– 31. 26451277 PMC4573182
  52. [58]Gao X, Salomon C, Freeman DJ. Extracellular Vesicles from Adipose Tissue-A Potential Role in Obesity and Type 2 Diabetes? Front Endocrinol (Lausanne) 2017; 8: 202. 28868048 PMC5563356
  53. [59]Park PH, Sanz-Garcia C, Nagy LE. Adiponectin as an anti-fibrotic and anti-inflammatory adipokine in the liver. Curr Pathobiol Rep 2015; 3: 243– 252. 26858914 PMC4743902
  54. [60]McCullough RL, McMullen MR, Poulsen KL, Anaphylatoxin Receptors C3aR and C5aR1 are important factors that influence the impact of ethanol on the adipose secretome. Frontiers Immunol 2018; in press. PMC6158367 30294325
  55. [61]Hajiasgharzadeh K, Baradaran B. Cholinergic Anti-Inflammatory Pathway and the Liver. Adv Pharm Bull 2017; 7: 507– 513. 29399541 PMC5788206
  56. [63]Massey VL, Beier JI, Ritzenthaler JD, Potential Role of the Gut/Liver/Lung Axis in Alcohol- Induced Tissue Pathology. Biomolecules 2015; 5: 2477– 503. 26437442 PMC4693244
  57. [64]Roh YS, Zhang B, Loomba R, TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration. Am J Physiol Gastrointest Liver Physiol 2015; 309: G30– 41. 25930080 PMC4491507
  58. [65]Seki E, De Minicis S, Osterreicher CH, TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 2007; 13: 1324– 32. 17952090
  59. [66]Sprenger H, Kaufmann A, Garn H, Induction of neutrophil-attracting chemokines in transforming rat hepatic stellate cells. Gastroenterology 1997; 113: 277– 85. 9207288
  60. [67]Hellerbrand C, Jobin C, Iimuro Y, Inhibition of NFkappaB in activated rat hepatic stellate cells by proteasome inhibitors and an IkappaB super-repressor. Hepatology 1998; 27: 1285– 95. 9581682
  61. [68]Petrasek J, Bala S, Csak T, IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J Clin Invest 2012; 122: 3476– 89. 22945633 PMC3461900
  62. [69]Han YP, Yan C, Zhou L, A matrix metalloproteinase-9 activation cascade by hepatic stellate cells in trans-differentiation in the three-dimensional extracellular matrix. J Biol Chem 2007; 282: 12928– 39. 17322299 PMC2376818
  63. [70]Khanova E, Wu R, Wang W, Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients. Hepatology 2017. PMC5906140 29108122
  64. [71]Shi J, Zhao Y, Wang K, Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 2015; 526: 660– 5. 26375003
  65. [72]Xu MJ, Zhou Z, Parker R, Targeting inflammation for the treatment of alcoholic liver disease. Pharmacol Ther 2017; 180: 77– 89. 28642119 PMC5677537
  66. [73]Szabo G Clinical Trial Design for Alcoholic Hepatitis. Semin Liver Dis 2017; 37: 332– 342. 29272895
  67. [74]Tilg H, Moschen AR, Szabo G. Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology 2016; 64: 955– 65. 26773297
  68. [75]Tang KY, Lickliter J, Huang ZH, Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects. Cell Mol Immunol 2018. PMC6474205 29670279
  69. [76]Ma HY, Xu J, Liu X, The role of IL-17 signaling in regulation of the liver-brain axis and intestinal permeability in Alcoholic Liver Disease. Curr Pathobiol Rep 2016; 4: 27– 35. 27239399 PMC4878828
  70. [77]Wieser V, Adolph TE, Enrich B, Reversal of murine alcoholic steatohepatitis by pepducin- based functional blockade of interleukin-8 receptors. Gut 2017; 66: 930– 938. 26858343 PMC5531226
  71. [78]Affo S, Morales-Ibanez O, Rodrigo-Torres D, CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis. Gut 2014; 63: 1782– 92. 24415562 PMC4092046
  72. [79]Gao B, Xu M. Chemokines and alcoholic hepatitis: are chemokines good therapeutic targets? Gut 2014; 63: 1683– 4. 24515805 PMC5451264
  73. [80]Cohen JI, Roychowdhury S, McMullen MR, Complement and alcoholic liver disease: Role of C1q in the pathogenesis of ethanol-induced liver injury in mice. Gastroenterology 2010: 664– 674. 20416309 PMC3273045
  74. [81]Pritchard MT, McMullen MR, Stavitsky AB, Differential contributions of C3, C5, and decay- accelerating factor to ethanol-induced fatty liver in mice. Gastroenterology 2007; 132: 1117– 26. 17383432 PMC1838572
  75. [82]Cresci GA, Allende D, McMullen MR, Alternative complement pathway component Factor D contributes to efficient clearance of tissue debris following acute CCl(4)-induced injury. Mol Immunol 2015; 64: 9– 17. 25467802 PMC4282836
  76. [83]McCullough RL, McMullen MR, Sheehan MM, Complement Factor D protects mice from ethanol-induced inflammation and liver injury. Am J Physiol Gastrointest Liver Physiol 2018; 315: G66– G79. 29597356 PMC6109707
  77. [84]Szabo G, Momen-Heravi F. Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets. Nat Rev Gastroenterol Hepatol 2017; 14: 455– 466. 28634412 PMC6380505
  78. [85]Cho YE, Song BJ, Akbar M, Extracellular vesicles as potential biomarkers for alcohol- and drug-induced liver injury and their therapeutic applications. Pharmacol Ther 2018; 187: 180– 194. 29621595 PMC5992092
  79. [86]Bala S, Csak T, Saha B, The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis. J Hepatol 2016; 64: 1378– 87. 26867493 PMC4874886
  80. [87]Saikia P, Bellos D, McMullen MR, MicroRNA 181b-3p and its target importin alpha5 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol. Hepatology 2017; 66: 602– 615. 28257601 PMC5519440
  81. [88]Satishchandran A, Ambade A, Rao S, MicroRNA 122, Regulated by GRLH2, Protects Livers of Mice and Patients From Ethanol-Induced Liver Disease. Gastroenterology 2018; 154: 238– 252 e7. 28987423 PMC5742049
  82. [89]Eguchi A, Lazaro RG, Wang J, Extracellular vesicles released by hepatocytes from gastric infusion model of alcoholic liver disease contain a MicroRNA barcode that can be detected in blood. Hepatology 2017; 65: 475– 490. 27639178 PMC5407075
  83. [90]Saha B, Momen-Heravi F, Furi I, Extracellular vesicles from mice with alcoholic liver disease carry a distinct protein cargo and induce macrophage activation through heat shock protein 90. Hepatology 2018; 67: 1986– 2000. 29251792 PMC5906190
  84. [91]Verma VK, Li H, Wang R, Alcohol stimulates macrophage activation through caspase- dependent hepatocyte derived release of CD40L containing extracellular vesicles. J Hepatol 2016; 64: 651– 60. 26632633 PMC4761285
  85. [92]Schwab A, Meyering SS, Lepene B, Extracellular vesicles from infected cells: potential for direct pathogenesis. Front Microbiol 2015; 6: 1132. 26539170 PMC4611157
  86. [93]Mancek-Keber M, Lainscek D, Bencina M, Extracellular vesicle-mediated transfer of constitutively active MyD88(L265P) engages MyD88(wt) and activates signaling. Blood 2018; 131: 1720– 1729. 29358175
  87. [94]Barteneva NS, Baiken Y, Fasler-Kan E, Extracellular vesicles in gastrointestinal cancer in conjunction with microbiota: On the border of Kingdoms. Biochim Biophys Acta 2017; 1868: 372– 393. 28669749
  88. [95]McCullough RL, McMullen MR, Das D, Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice. Mol Immunol 2016; 75: 122– 32. 27280845 PMC4939119
  89. [96]Zhou H, Yu M, Zhao J, IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease. Hepatology 2016; 64: 1978– 1993. 27628766 PMC5115953
  90. [97]Thakur V, Pritchard MT, McMullen MR, 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. J Leukoc Biol 2006; 79: 1348– 56. 16554353 PMC1959405
  91. [98]Saikia P, Roychowdhury S, Bellos D, Hyaluronic acid 35 normalizes TLR4 signaling in Kupffer cells from ethanol-fed rats via regulation of microRNA291b and its target Tollip. Sci Rep 2017; 7: 15671. 29142263 PMC5688113
  92. [99]Bala S, Marcos M, Kodys K, Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor {alpha} (TNF{alpha}) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem 2011; 286: 1436– 44. 21062749 PMC3020752
  93. [100]Wang J, Kainrad N, Shen H, Hepatic Knockdown of Splicing Regulator Slu7 Ameliorates Inflammation and Attenuates Liver Injury in Ethanol-Fed Mice. Am J Pathol 2018; 188: 1807– 1819. 29870742 PMC6099363
  94. [101]Avila DV, Barker DF, Zhang J, Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis. J Pathol 2016; 240: 96– 107. 27287961 PMC4993672
  95. [102]Gobejishvili L, Avila DV, Barker DF, S-adenosylmethionine decreases lipopolysaccharide- induced phosphodiesterase 4B2 and attenuates tumor necrosis factor expression via cAMP/protein kinase A pathway. J Pharmacol Exp Ther 2011; 337: 433– 43. 21266552 PMC3083110
  96. [103]Ju C, Tacke F. Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies. Cell Mol Immunol 2016; 13: 316– 27. 26908374 PMC4856798
  97. [104]Stoy S, Sandahl TD, Dige AK, Highest frequencies of interleukin-22-producing T helper cells in alcoholic hepatitis patients with a favourable short-term course. PLoS One 2013; 8: e55101. 23372820 PMC3555927
  98. [105]Ortiz V, Wands JR. Chronic ethanol diet increases regulatory T-cell activity and inhibits hepatitis C virus core-specific cellular immune responses in mice. Hepatol Res 2014; 44: 788– 97. 23710581 PMC3883867
  99. [106]Maricic I, Sheng H, Marrero I, Inhibition of type I natural killer T cells by retinoids or following sulfatide-mediated activation of type II natural killer T cells attenuates alcoholic liver disease in mice. Hepatology 2015; 61: 1357– 69. 25477000 PMC4376634
  100. [108]Li H, Feng D, Cai Y, Hepatocytes and neutrophils cooperatively suppress bacterial infection by differentially regulating lipocalin-2 and neutrophil extracellular traps. Hepatology 2018. PMC6173649 29633303
  101. [109]Zhou Z, Xu MJ, Cai Y, Neutrophil-Hepatic Stellate Cell Interactions Promote Fibrosis in Experimental Steatohepatitis. Cell Mol Gastroenterol Hepatol 2018; 5: 399– 413. 29552626 PMC5852390
  102. [110]Weiskirchen R, Tacke F. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology. Hepatobiliary Surg Nutr 2014; 3: 344– 63. 25568859 PMC4273119

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Authors
Gao, B., Ahmad, M. F., Nagy, L. E., & Tsukamoto, H.
Affiliations
  • National Institutes of Health (US)
  • Cleveland Clinic Lerner College of Medicine (US)
  • Cleveland Clinic (US)
  • University of Southern California (US)
Corresponding author
  • Gao, Bin
  • Nagy, Laura E.
  • Tsukamoto, Hidekazu
ORCID
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
2019-02
Volume
70
Issue
2
Pages
249-259
ISSN
0168-8278 (ISSN-L)
DOI
10.1016/j.jhep.2018.10.023
PMC
PMC6361545
OpenAlex
W2910709942
Cited by
392
References
7
Citations by year
2026: 45 · 2025: 62 · 2024: 54 · 2023: 61 · 2022: 56 · 2021: 45 · 2020: 52 · 2019: 16 · 2017: 1
FWCI
6.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (P50 AA024333, U01AA021890, RO1AA023722, P50AA011999, U01AA018663, R24AA012885, I01BX001991, IK6BX004205)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
alcoholic steatohepatitis, liver inflammation, alcoholic hepatitis, gut dysbiosis, intestinal barrier integrity, hepatocyte inflammation, damage-associated molecular patterns, cytokines and chemokines, macrophages, monocytes, innate and adaptive immunity, extracellular vesicles, microRNA, organ crosstalk, liver repair, bacterial infection
MeSH terms
Gastrointestinal Microbiome, Ethanol, Animals, Fatty Liver, Alcoholic, Hepatitis, Alcoholic, Humans, Inflammation, Kupffer Cells, Neutrophils, T-Lymphocytes, Inflammation Mediators, Hepatocytes, Dysbiosis

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