Acetic acid alleviates the inflammatory response and liver injury in septic mice by increasing the expression of TRIM40

Yang,Hongguang; Meng,Lan; Ai,Dengbin; Hou,Nianguo; Li,Hui; Shuai,Xunjun; Peng,Xiaoyan

doi:10.3892/etm.2019.7274

Acetic acid alleviates the inflammatory response and liver injury in septic mice by increasing the expression of TRIM40

Authors:
- Hongguang Yang
- Lan Meng
- Dengbin Ai
- Nianguo Hou
- Hui Li
- Xunjun Shuai
- Xiaoyan Peng
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Affiliations: Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
Published online on: February 13, 2019 https://doi.org/10.3892/etm.2019.7274
Pages: 2789-2798

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Abstract

Sepsis remains a significant health care issue in clinical practice due to its high mortality rate and healthcare cost, despite extensive efforts to better understand the pathophysiology of sepsis. The systemic inflammatory response often leads to severe liver injury, even acute liver dysfunction and failure. Acetic acid, as a type of chemical compound, has been reported to be an emerging drug for improving metabolic syndrome and inhibiting inflammation in rats and human. To verify the effects of acetic acid in protecting the liver and reducing the inflammatory response, a septic mouse model was established by cecal ligation and puncture (CLP), and then the CLP‑model mice were treated with acetic acid or PBS. Following the treatment, it was determined that, in CLP‑model mice, acetic acid could alleviate the inflammatory response by decreasing the expression of cytokines including interleukin‑6 and tumor necrosis factor‑α. Additionally, acetic acid also alleviated the liver injury, and the levels of alanine aminotransaminase, aspartate aminotransferase, Toll‑like receptor (TLR)4 and nuclear factor‑κB (NF‑κB) were decreased. The expression of tripartite motif‑containing protein (TRIM)40 was also upregulated significantly. Therefore, the authors of the current study hypothesized that acetic acid could decrease the inflammatory response by increasing the expression of TRIM40 and TRIM40 may regulate the activity of the TLR4 signaling pathway. To further illustrate the interaction between TRIM40 and the TLR4 signaling pathway, the authors collected macrophages from the peritoneal cavity by intraperitoneally administering mice with 5 ml ice‑cold normal saline. Following the collection, peritoneal macrophages were treated with acetic acid, TRIM40 small interfering RNA or PBS. It was demonstrated that acetic acid upregulated the expression of TRIM40. When TRIM40 was silenced, the protective effect of acetic acid would be reversed as well. The results suggested that TRIM40 could act on and downregulate the activity of the TLR4 signaling pathway. TRIM40 is possibly the major target for acetic acid, which may function as a protective factor in septic mice.

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1	Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al: The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 315:801–810. 2016. View Article : Google Scholar : PubMed/NCBI
2	Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, et al: Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 41:580–637. 2013. View Article : Google Scholar : PubMed/NCBI
3	Dombrovskiy VY, Martin AA, Sunderram J and Paz HL: Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003. Crit Care Med. 35:1244–1250. 2007. View Article : Google Scholar : PubMed/NCBI
4	Martin-Loeches I, Levy MM and Artigas A: Management of severe sepsis: Advances, challenges, and current status. Drug Des Devel Ther. 9:2079–2088. 2015. View Article : Google Scholar : PubMed/NCBI
5	Sagy M, Al-Qaqaa Y and Kim P: Definitions and pathophysiology of sepsis. Curr Probl Pediatr Adolesc Health Care. 43:260–263. 2013. View Article : Google Scholar : PubMed/NCBI
6	Gotts JE and Matthay MA: Sepsis: Pathophysiology and clinical management. BMJ. 353:i15852016. View Article : Google Scholar : PubMed/NCBI
7	Vincent JL, Marshall JC, Namendys-Silva SA, Francois B, Martin-Loeches I, Lipman J, Reinhart K, Antonelli M, Pickkers P, Njimi H, et al: Assessment of the worldwide burden of critical illness: The intensive care over nations (ICON) audit. Lancet Respir Med. 2:380–386. 2014. View Article : Google Scholar : PubMed/NCBI
8	Adhikari NK, Fowler RA, Bhagwanjee S and Rubenfeld GD: Critical care and the global burden of critical illness in adults. Lancet. 376:1339–1346. 2010. View Article : Google Scholar : PubMed/NCBI
9	Torio CM and Moore BJ: National inpatient hospital costs: The most expensive conditions by payer, 2013. HCUP Statistical Brief #204. Agency for Healthcare Research and Quality; Rockville, MD: 2016, https://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-ExpensiveHospital-Conditions.jspApril 28–2016
10	Angus DC and van der Poll T: Severe sepsis and septic shock. N Engl J Med. 369:840–851. 2013. View Article : Google Scholar : PubMed/NCBI
11	Blanco J, Muriel-Bombin A, Sagredo V, Taboada F, Gandia F, Tamayo L, Collado J, Garcia-Labattut A, Carriedo D, Valledor M, et al: Incidence, organ dysfunction and mortality in severe sepsis: A Spanish multicentre study. Crit Care. 12:R1582008. View Article : Google Scholar : PubMed/NCBI
12	Nesseler N, Launey Y, Aninat C, Morel F, Malledant Y and Seguin P: Clinical review: The liver in sepsis. Crit Care. 16:2352012. View Article : Google Scholar : PubMed/NCBI
13	Brun-Buisson C, Meshaka P, Pinton P and Vallet B; EPISEPSIS Study Group, : EPISEPSIS: A reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 30:580–588. 2004. View Article : Google Scholar : PubMed/NCBI
14	Bakker J, Grover R, McLuckie A, Holzapfel L, Andersson J, Lodato R, Watson D, Grossman S, Donaldson J and Takala J: Administration of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: Results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Crit Care Med. 32:1–12. 2004. View Article : Google Scholar : PubMed/NCBI
15	Bellou A, Schaub B, Ting L and Finn PW: Toll receptors modulate allergic responses: Interaction with dendritic cells, T cells and mast cells. Curr Opin Allergy Clin Immunol. 3:487–494. 2003. View Article : Google Scholar : PubMed/NCBI
16	Biswas SK and Lopez-Collazo E: Endotoxin tolerance: New mechanisms, molecules and clinical significance. Trends Immunol. 30:475–487. 2009. View Article : Google Scholar : PubMed/NCBI
17	Zhang S, Yang N, Ni S, Li W, Xu L, Dong P and Lu M: Pretreatment of lipopolysaccharide (LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway. Int J Clin Exp Pathol. 7:6626–6634. 2014.PubMed/NCBI
18	Zhang YP, Pan CS, Yan L, Liu YY, Hu BH, Chang X, Li Q, Huang DD, Sun HY, Fu G, et al: Catalpol restores LPS-elicited rat microcirculation disorder by regulation of a network of signaling involving inhibition of TLR-4 and SRC. Am J Physiol Gastrointest Liver Physiol. 311:G1091–G1104. 2016. View Article : Google Scholar : PubMed/NCBI
19	Tissieres P, Dunn-Siegrist I, Schappi M, Elson G, Comte R, Nobre V and Pugin J: Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria. Blood. 111:2122–2131. 2008. View Article : Google Scholar : PubMed/NCBI
20	Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, et al: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science. 282:2085–2088. 1998. View Article : Google Scholar : PubMed/NCBI
21	Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, et al: The tripartite motif family identifies cell compartments. EMBO J. 20:2140–2151. 2001. View Article : Google Scholar : PubMed/NCBI
22	Hatakeyama S: TRIM proteins and cancer. Nat Rev Cancer. 11:792–804. 2011. View Article : Google Scholar : PubMed/NCBI
23	Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S and Jung JU: TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 446:916–920. 2007. View Article : Google Scholar : PubMed/NCBI
24	Miyajima N, Maruyama S, Bohgaki M, Kano S, Shigemura M, Shinohara N, Nonomura K and Hatakeyama S: TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells. Cancer Res. 68:3486–3494. 2008. View Article : Google Scholar : PubMed/NCBI
25	Kikuchi M, Okumura F, Tsukiyama T, Watanabe M, Miyajima N, Tanaka J, Imamura M and Hatakeyama S: TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells. Biochim Biophys Acta. 1793:1828–1836. 2009. View Article : Google Scholar : PubMed/NCBI
26	Institute of Laboratory Animal Resources (U.S.) Committee on Care Use of Laboratory Animals National Institutes of Health (U.S.) Division of Research Resources. Guide for the Care and Use of Laboratory Animals. NIH Publication. pp. 85–23. U.S. Dept. of Health and Human Services, Public Health Service, National Insititutes of Health; Bethesda, MD: 1985
27	National Research Council (US) Institute for Laboratory Animal Research: Guide for the Care and Use of Laboratory Animals. National Academies Press (US); Washington, DC: 1996
28	Kawakami T, Koike A and Amano F: Induction of different activated phenotypes of mouse peritoneal macrophages grown in different tissue culture media. Cytotechnology. 69:631–642. 2017. View Article : Google Scholar : PubMed/NCBI
29	Awasthi A, Rathore G, Sood N, Khan MY and Lakra WS: Establishment of a leukocyte cell line derived from peritoneal macrophages of fish, Labeo rohita (Hamilton, 1822). Cytotechnology. 67:85–96. 2015. View Article : Google Scholar : PubMed/NCBI
30	Rittirsch D, Huber-Lang MS, Flierl MA and Ward PA: Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 4:31–36. 2009. View Article : Google Scholar : PubMed/NCBI
31	Lemaitre E, Allee C, Vabret A, Eterradossi N and Brown PA: Single reaction, real time RT-PCR detection of all known avian and human metapneumoviruses. J Virol Methods. 251:61–68. 2018. View Article : Google Scholar : PubMed/NCBI
32	Ott LE and Carson S: Immunological tools: Engaging students in the use and analysis of flow cytometry and enzyme-linked immunosorbent assay (ELISA). Biochem Mol Biol Educ. 42:382–397. 2014. View Article : Google Scholar : PubMed/NCBI
33	Beh BK, Mohamad NE, Yeap SK, Ky H, Boo SY, JYH C, Tan SW, Ho WY, Sharifuddin SA, Long K and Alitheen NB: Anti-obesity and anti-inflammatory effects of synthetic acetic acid vinegar and Nipa vinegar on high-fat-diet-induced obese mice. Sci Rep. 7:66642017. View Article : Google Scholar : PubMed/NCBI
34	Yamashita H: Biological function of acetic acid-improvement in obesity and glucose tolerance by acetic acid in type 2 diabetic rats. Crit Rev Food Sci Nutr. 56:S171–S175. 2016. View Article : Google Scholar : PubMed/NCBI
35	Mohamad NE, Yeap SK, Lim KL, Yusof HM, Beh BK, Tan SW, Ho WY, Sharifuddin SA, Jamaluddin A, Long K, et al: Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice. Chin Med. 10:32015. View Article : Google Scholar : PubMed/NCBI
36	Beh BK, Mohamad NE, Yeap SK, Lim KL, Wang YH, Yusof HM, Sharifuddin SA, Jamaluddin A, Long K and Alitheen NB: Polyphenolic profiles and the in vivo antioxidant effect of nipa vinegar on paracetamol induced liver damage. RSC Advance. 6:63304–63313. 2016. View Article : Google Scholar
37	Ouchi N and Walsh K: Adiponectin as an anti-inflammatory factor. Clin Chim Acta. 380:24–30. 2007. View Article : Google Scholar : PubMed/NCBI
38	Noguchi K, Okumura F, Takahashi N, Kataoka A, Kamiyama T, Todo S and Hatakeyama S: TRIM40 promotes neddylation of IKKgamma and is downregulated in gastrointestinal cancers. Carcinogenesis. 32:995–1004. 2011. View Article : Google Scholar : PubMed/NCBI
39	Jekarl DW, Kim JY, Lee S, Kim M, Kim Y, Han K, Woo SH and Lee WJ: Diagnosis and evaluation of severity of sepsis via the use of biomarkers and profiles of 13 cytokines: A multiplex analysis. Clin Chem Lab Med. 53:575–581. 2015. View Article : Google Scholar : PubMed/NCBI
40	Liang Y, Li X, Zhang X, Li Z, Wang L, Sun Y, Liu Z and Ma X: Elevated levels of plasma TNF-alpha are associated with microvascular endothelial dysfunction in patients with sepsis through activating the NF-kappaB and p38 mitogen-activated protein kinase in endothelial cells. Shock. 41:275–281. 2014. View Article : Google Scholar : PubMed/NCBI
41	Khakpour S, Wilhelmsen K and Hellman J: Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate Immun. 21:827–846. 2015. View Article : Google Scholar : PubMed/NCBI
42	Chantratita N, Tandhavanant S, Seal S, Wikraiphat C, Wongsuvan G, Ariyaprasert P, Suntornsut P, Teerawattanasook N, Jutrakul Y, Srisurat N, et al: TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis. Clin Microbiol Infect. 23:47.e1–47.e10. 2017. View Article : Google Scholar
43	Chan CC, Lee KC, Huang YH, Chou CK, Lin HC and Lee FY: Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury. J Gastroenterol Hepatol. 29:603–613. 2014. View Article : Google Scholar : PubMed/NCBI
44	Weighardt H and Holzmann B: Role of Toll-like receptor responses for sepsis pathogenesis. Immunobiology. 212:715–722. 2007. View Article : Google Scholar : PubMed/NCBI
45	Tian Y, Li Z, Shen B, Zhang Q and Feng H: Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-kappaB and activating Nrf2/HO-1 signaling pathways. Int Immunopharmacol. 45:148–155. 2017. View Article : Google Scholar : PubMed/NCBI
46	Feng H, Chen J, Wang H, Cheng Y, Zou Z, Zhong Q and Xu J: Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice. Lab Invest. 97:1008–1019. 2017. View Article : Google Scholar : PubMed/NCBI