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Effects of 5,14-HEDGE, a 20-HETE mimetic, on lipopolysaccharide-induced changes in MyD88/TAK1/IKKβ/IκB-α/NF-κB pathway and circulating miR-150, miR-223, and miR-297 levels in a rat model of septic shock

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Abstract

Objectives

We have previously demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), which mimics the effects of endogenously produced 20-HETE, prevents vascular hyporeactivity, hypotension, tachycardia, inflammation, and mortality in a rodent model of septic shock. The present study was performed to determine whether decreased renal and cardiovascular expression and activity of myeloid differentiation factor 88 (MyD88)/transforming growth factor-activated kinase 1 (TAK1)/inhibitor of κB (IκB) kinase β (IKKβ)/IκB-α/nuclear factor-κB (NF-κB) pathway and reduced circulating microRNA (miR)-150, miR-223, and miR-297 expression levels participate in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation in response to systemic administration of lipopolysaccharide (LPS).

Methods

Conscious male Wistar rats received saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. Separate groups of LPS-treated rats were given 5,14-HEDGE (30 mg/kg) 1 h after injection of saline or LPS. The rats were killed 4 h after LPS challenge and blood, kidney, heart, thoracic aorta, and superior mesenteric artery were collected for measurement of the protein expression.

Results

LPS-induced fall in blood pressure and rise in heart rate were associated with increased MyD88 expression and phosphorylation of TAK1 and IκB-α in cytosolic fractions of the tissues. LPS also caused an increase in both unphosphorylated and phosphorylated NF-κB p65 proteins in the cytosolic and nuclear fractions as well as nuclear translocation of NF-κB p65. In addition, serum miR-150, miR-223, and miR-297 expression levels were increased in LPS-treated rats. These effects of LPS were prevented by 5,14-HEDGE.

Conclusions

These results suggest that downregulation of MyD88/TAK1/IKKβ/IκB-α/NF-κB pathway as well as decreased circulating miR-150, miR-223, and miR-297 expression levels participate in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation in the rat model of septic shock.

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Abbreviations

20-HETE:

20-Hydroxyeicosatetraenoic acid

5,14-HEDGE:

N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine

AP:

Activating protein

BSA:

Bovine serum albumin

CD:

Cluster of differentiation

DNA:

Complementary deoxyribonucleic acid

COX:

Cyclooxygenase

CT:

Comperative threshold cycle

CYP:

Cyctochrome P450

EET:

Epoxyeicosatrienoic acid

ERK:

Extracellular signal-regulated kinase

HR:

Heart rate

IKK:

IκB kinase

IκB:

Inhibitor of κb

IL:

Interleukin

i.p.:

Intraperitoneally

IRAK:

IL-1 receptor-associated kinase

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

MAP:

Mean arterial pressure

MAPK:

Mitogen-activated protein kinase

MD:

Myeloid differentiation protein

MEK:

MAP kinase

MKK:

MAPK kinase

miRNA:

MicroRNA

mRNA:

Messenger RNA

MyD88:

Myeloid differentiation factor 88

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF-κB:

Nuclear factor-κB

NIK:

NF-κB-inducing kinase

NO:

Nitric oxide

PG:

Prostaglandin

PKC:

Protein kinase C

PKG:

Protein kinase

RNA:

Ribonucleic acid

qRT-PCR:

Quantitative real-time polymerase chain reaction

s.c.:

Subcutaneously

sEH:

Soluble epoxide hydrolase

sGC:

Soluble guanylyl cyclase

SIRS:

Systemic inflammatory response syndrome

TAK:

Transforming growth factor-activated kinase

TIRAP:

Toll-interleukin-1 receptor domain containing adaptor protein

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TRAF:

TNF receptor-associated factor

References

  1. Kroetz DL, Xu F. Regulation and inhibition of arachidonic acid omega-hydroxylases and 20-HETE formation. Annu Rev Pharmacol Toxicol. 2005;45:413–38.

    Article  CAS  PubMed  Google Scholar 

  2. Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev. 2002;82:131–85.

    CAS  PubMed  Google Scholar 

  3. Tunctan B, Korkmaz B, Sari AN, Kacan M, Unsal D, Serin MS, Buharalioglu CK, Sahan-Firat S, Schunck WH, Falck JR, Malik KU. A novel treatment strategy for sepsis and septic shock based on the interactions between prostanoids, nitric oxide, and 20-hydroxyeicosatetraenoic acid. Antiinflamm Antiallergy Agents Med Chem. 2012;11:121–50.

    CAS  PubMed  Google Scholar 

  4. Escalante B, Omata K, Sessa W, Lee SG, Falck JR, Schwartzman ML. 20-hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries. Eur J Pharmacol. 1993;235:1–7.

    Article  CAS  PubMed  Google Scholar 

  5. Escalante B, Sessa WC, Falck JR, Yadagiri P, Schwartzman ML. Vasoactivity of 20-hydroxyeicosatetraenoic acid is dependent on metabolism by cyclooxygenase. J Pharmacol Exp Ther. 1989;248:229–32.

    CAS  PubMed  Google Scholar 

  6. Randriamboavonjy V, Busse R, Fleming I. 20-HETE-induced contraction of small coronary arteries depends on the activation of Rho-kinase. Hypertension. 2003;41:801–6.

    Article  CAS  PubMed  Google Scholar 

  7. Schwartzman ML, Falck JR, Yadagiri P, Escalante B. Metabolism of 20-hydroxyeicosatetraenoic acid by cyclooxygeanse: formation and identification of novel endothelium-dependent vasoconstrictor metabolites. J Biol Chem. 1989;264:11658–62.

    CAS  PubMed  Google Scholar 

  8. Zou AP, Fleming JT, Falck JR, Jacobs ER, Gebremedhin D, Harder DR, Roman RJ. 20-HETE is an endogenous inhibitor of the large-conductance Ca(2+)-activated K+ channel in renal arterioles. Am J Physiol. 1996;270:R228–37.

    CAS  PubMed  Google Scholar 

  9. Akbulut T, Regner KR, Roman RJ, Avner ED, Falck JR, Park F. 20-HETE activates the Raf/MEK/ERK pathway in renal epithelial cells through an EGFR- and c-Src-dependent mechanism. Am J Physiol. 2009;297:F662–70.

    Article  CAS  Google Scholar 

  10. Ponnoth DS, Nayeem MA, Kunduri SS, Tilley SL, Zeldin DC, Ledent C, Mustafa SJ. Role of ω-hydroxylase in adenosine-mediated aortic response through MAP kinase using A2A-receptor knockout mice. Am J Physiol. 2012;302:R400–8.

    CAS  Google Scholar 

  11. Sun CW, Falck JR, Harder DR, Roman RJ. Role of tyrosine kinase and PKC in the vasoconstrictor response to 20-HETE in renal arterioles. Hypertension. 1999;33:414–8.

    Article  CAS  PubMed  Google Scholar 

  12. Carroll MA, Capparelli MF, Doumand AB, Cheng MK, Jiang H, McGiff JC. Renal vasoactive eicosanoids: interactions between cytochrome P450 and cyclooxygenase metabolites during salt depletion. Am J Hypertens. 2001;14:159A.

    Article  Google Scholar 

  13. Carroll MA, Garcia MP, Falck JR, McGiff JC. Cyclooxygenase dependency of the renovascular actions of cytochrome P450-derived arachidonate metabolites. J Pharmacol Exp Ther. 1992;260:104–9.

    CAS  PubMed  Google Scholar 

  14. Pratt PF, Falck JR, Reddy KM, Kurian JB, Campbell WB. 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension. 1998;31:237–41.

    Article  CAS  PubMed  Google Scholar 

  15. Yu M, McAndrew RP, Al-Saghir R, Maier KG, Medhora M, Roman RJ, Jacobs ER. Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries. J Appl Physiol. 2002;93:1391–9.

    CAS  PubMed  Google Scholar 

  16. Fang X, Faraci FM, Kaduce TL, Harmon S, Modrick ML, Hu S, Moore SA, Falck JR, Weintraub NL, Spector AA. 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase. Am J Physiol. 2006;291:H2301–7.

    CAS  Google Scholar 

  17. Cheng J, Wu CC, Gotlinger KH, Zhang F, Falck JR, Narsimhaswamy D, Schwartzman ML. 20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling. J Pharmacol Exp Ther. 2010;332:57–65.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Ishizuka T, Cheng J, Singh H, Vitto MD, Manthati VL, Falck JR, Laniado-Schwartzman M. 20-Hydroxyeicosatetraenoic acid stimulates nuclear factor-κB activation and the production of inflammatory cytokines in human endothelial cells. J Pharmacol Exp Ther. 2008;324:103–10.

    Article  CAS  PubMed  Google Scholar 

  19. Anwar-mohamed A, Zordoky BN, Aboutabl ME, El-Kadi AO. Alteration of cardiac cytochrome P450-mediated arachidonic acid metabolism in response to lipopolysaccharide-induced acute systemic inflammation. Pharmacol Res. 2010;61:410–8.

    Article  CAS  PubMed  Google Scholar 

  20. Theken KN, Deng Y, Kannon MA, Miller TM, Poloyac SM, Lee CR. Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism. Drug Metab Dispos. 2011;39:22–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Landström M. The TAK1-TRAF6 signalling pathway. Int J Biochem Cell Biol. 2010;42:585–9.

    PubMed  Google Scholar 

  22. Liu SF, Malik AB. NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am J Physiol. 2006;290:L622–45.

    Article  CAS  Google Scholar 

  23. Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–51.

    Article  CAS  PubMed  Google Scholar 

  24. Gupta SC, Sundaram C, Reuter S, Aggarwal BB. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta. 2010;1799:775–87.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Lee HJ. Exceptional stories of microRNAs. Exp Biol Med. 2013;238:339–43.

    Article  Google Scholar 

  26. Liu B, Li J, Cairns MJ. Identifying miRNAs, targets and functions. Brief Bioinform. 2012;15(1):1–19.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Ul Hussain M. Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action. Cell Tissue Res. 2012;349:405–13.

    Article  PubMed  Google Scholar 

  28. Abdellatif M. Differential expression of microRNAs in different disease states. Circ Res. 2012;110:638–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. O’Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol. 2012;30:295–312.

    Article  PubMed  Google Scholar 

  30. Raisch J, Darfeuille-Michaud A, Nguyen HT. Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol. 2013;19:2985–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Rebane A, Akdis CA. MicroRNAs: essential players in the regulation of inflammation. J Allergy Clin Immunol. 2013;132:15–26.

    Article  CAS  PubMed  Google Scholar 

  32. Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol. 2011;80:193–208.

    Article  PubMed  Google Scholar 

  33. Velu VK, Ramesh R, Srinivasan AR. Circulating microRNAs as biomarkers in health and disease. J Clin Diagn Res. 2012;6:1791–5.

    PubMed Central  PubMed  Google Scholar 

  34. Wang JF, Yu ML, Yu G, Bian JJ, Deng XM, Wan XJ, Zhu KM. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun. 2010;394:184–8.

    Article  CAS  PubMed  Google Scholar 

  35. Vasilescu C, Rossi S, Shimizu M, Tudor S, Veronese A, Ferracin M, et al. MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis. PLoS One. 2009;4:e7405.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Wang H, Meng K, Chen WJ, Feng D, Jia Y, Xie L. Serum miR-574-5p: a prognostic predictor of sepsis patients. Shock. 2012;37:263–7.

    Article  CAS  PubMed  Google Scholar 

  37. Schmidt WM, Spiel AO, Jilma B, Wolzt M, Müller M. In vivo profile of the human leukocyte microRNA response to endotoxemia. Biochem Biophys Res Commun. 2009;380(3):437–41.

    Article  CAS  PubMed  Google Scholar 

  38. Karolina DS, Armugam A, Tavintharan S, Wong MT, Lim SC, Sum CF, Jeyaseelan K. MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PLoS One. 2011;6:e22839.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Venugopal SK, Jiang J, Kim TH, Li Y, Wang SS, Torok NJ, Wu J, Zern MA. Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation. Am J Physiol. 2010;298:G101–6.

    Article  CAS  Google Scholar 

  40. Lu H, Buchan RJ, Cook SA. MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res. 2010;86:410–20.

    Article  CAS  PubMed  Google Scholar 

  41. Davidson LA, Wang N, Shah MS, Lupton JR, Ivanov I, Chapkin RS. n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon. Carcinogenesis. 2009;30:2077–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Cuez T, Korkmaz B, Buharalioglu CK, Sahan-Firat S, Falck J, Malik KU, Tunctan B. A synthetic analogue of 20-HETE, 5,14-HEDGE, reverses endotoxin-induced hypotension via increased 20-HETE levels associated with decreased iNOS protein expression and vasodilator prostanoid production in rats. Basic Clin Pharmacol. 2010;106:378–88.

    Article  CAS  Google Scholar 

  43. Tunctan B, Korkmaz B, Buharalioglu CK, Sahan Firat S, Anjaiah S, Falck J, Roman RJ, Malik KU. A 20-HETE agonist, N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine, opposes the fall in blood pressure and vascular reactivity in endotoxin-treated rats. Shock. 2008;30:329–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Tunctan B, Korkmaz B, Sari AN, Kacan M, Unsal D, Serin MS, Buharalioglu CK, Sahan-Firat S, Cuez T, Schunck WH, Manthati VL, Falck JR, Malik KU. Contribution of iNOS/sGC/PKG pathway, COX-2, CYP4A1, and gp91phox to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against vasodilation, hypotension, tachycardia, and inflammation in a rat model of septic shock. Nitric Oxide. 2013;33:18–41.

    Article  CAS  PubMed  Google Scholar 

  45. Tunctan B, Korkmaz B, Sari AN, Kacan M, Unsal D, Serin MS, Buharalioglu CK, Sahan-Firat S, Cuez T, Schunck WH, Falck JR, Malik KU. 5,14-HEDGE, a 20-HETE mimetic, reverses hypotension and improves survival in a rodent model of septic shock: contribution of soluble epoxide hydrolase, CYP2C23, MEK1/ERK1/2/IKKβ/IκB-α/NF-κB pathway, and proinflammatory cytokine formation. Prostaglandins Other Lipid Mediat. 2013;102–103:31–41.

    Article  PubMed  Google Scholar 

  46. Gadjeva M, Tomczak MF, Zhang M, Wang YY, Dull K, Rogers AB, Erdman SE, Fox JG, Carroll M, Horwitz BH. A role for NF-kappa B subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock. J Immunol. 2004;173:5786–93.

    Article  CAS  PubMed  Google Scholar 

  47. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol. 2007;8:49–62.

    Article  CAS  PubMed  Google Scholar 

  48. Schomer-Miller B, Higashimoto T, Lee YK, Zandi E. Regulation of IkappaB kinase (IKK) complex by IKKgamma-dependent phosphorylation of the T-loop and C terminus of IKKbeta. J Biol Chem. 2006;281:15268–76.

    Article  CAS  PubMed  Google Scholar 

  49. Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell. 1997;91:243–52.

    Article  CAS  PubMed  Google Scholar 

  50. Jiang X, Takahashi N, Matsui N, Tetsuka T, Okamoto T. The NF-kappa B, activation in lymphotoxin beta receptor signaling depends on the phosphorylation of p65 at serine 536. J Biol Chem. 2003;278:919–26.

    Article  CAS  PubMed  Google Scholar 

  51. Mattioli I, Sebald A, Bucher C, Charles RP, Nakano H, Doi T, Kracht M, Schmitz ML. Transient and selective NF-kappa B p65 serine 536 phosphorylation induced by T cell costimulation is mediated by I kappa B kinase beta and controls the kinetics of p65 nuclear import. J Immunol. 2004;172:6336–44.

    Article  CAS  PubMed  Google Scholar 

  52. Sakurai H, Chiba H, Miyoshi H, Sugita T, Toriumi W. IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain. J Biol Chem. 1999;274:30353–6.

    Article  CAS  PubMed  Google Scholar 

  53. Yang F, Tang E, Guan K, Wang CY. IKK beta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide. J Immunol. 2003;170:5630–5.

    Article  CAS  PubMed  Google Scholar 

  54. Chew J, Biswas S, Shreeram S, Humaidi M, Wong ET, Dhillion MK, Teo H, Hazra A, Fang CC, López-Collazo E, Bulavin DV, Tergaonkar V. WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol. 2009;11:659–66.

    CAS  PubMed  Google Scholar 

  55. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109:S81–96.

    Article  CAS  PubMed  Google Scholar 

  56. Birbach A, Gold P, Binder BR, Hofer E, de Martin R, Schmid JA. Signaling molecules of the NF-kappa B pathway shuttle constitutively between cytoplasm and nucleus. J Biol Chem. 2002;277:10842–51.

    Article  CAS  PubMed  Google Scholar 

  57. Huang TT, Kudo N, Yoshida M, Miyamoto S. A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes. Proc Natl Acad Sci USA. 2000;97:1014–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Johnson C, Van Antwerp D, Hope TJ. An N-terminal nuclear export signal is required for the nucleocytoplasmic shuttling of IkappaBalpha. EMBO J. 1999;18:6682–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Shirakawa F, Mizel SB. In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol Cell Biol. 1989;9:2424–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Iida A, Yoshidome H, Shida T, Takano S, Takeuchi D, Kimura F, Shimizu H, Ohtsuka M, Miyazaki M. Hepatocyte nuclear factor-kappa beta (NF-kappaB) activation is protective but is decreased in the cholestatic liver with endotoxemia. Surgery. 2010;148:477–89.

    Article  PubMed  Google Scholar 

  61. Jiang Q, Liu P, Wu X, Liu W, Shen X, Lan T, Xu S, Peng J, Xie X, Huang H. Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: involvement of NF-κB signaling pathway. Mol Cell Endocrinol. 2011;331:34–40.

    Article  CAS  PubMed  Google Scholar 

  62. Kwon WY, Suh GJ, Kim KS, Kwak YH. Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-κB pathway. Crit Care Med. 2011;39:328–34.

    CAS  PubMed  Google Scholar 

  63. Meyer-Schwesinger C, Dehde S, von Ruffer C, Gatzemeier S, Klug P, Wenzel UO, Stahl RA, Thaiss F, Meyer TN. Rho kinase inhibition attenuates LPS-induced renal failure in mice in part by attenuation of NF-kappaB p65 signaling. Am J Physiol. 2009;296:F1088–99.

    Article  CAS  Google Scholar 

  64. Zhang X, Song Y, Ci X, An N, Ju Y, Li H, Wang X, Han C, Cui J, Deng X. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res. 2008;57:524–9.

    Article  CAS  PubMed  Google Scholar 

  65. Boldin MP, Baltimore D. MicroRNAs, new effectors and regulators of NF-κB. Immunol Rev. 2012;246:205–20.

    Article  PubMed  Google Scholar 

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Acknowledgments

Financial support was provided by grants from Mersin University (BAP-SBE EMBB [ANS] 2012-4 DR), the Robert A. Welch Foundation (GL625910), and NIH (HLBI-19134-38 ve GM31278). The results of this study were included in the Ph.D. thesis of Pharm. M.S. Ayse Nihal SARI. We greatly acknowledge Pharm. Meryem TEMIZ and Engin KAPLAN for their assistance in the study.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Yenisehir Campus, Mersin University, 33169, Mersin, Turkey

    A. Nihal Sari, Belma Korkmaz, Meltem Kacan, Demet Unsal, C. Kemal Buharalioglu, Seyhan Sahan Firat & Bahar Tunctan

  2. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Mersin University, Mersin, Turkey

    Mehmet Sami Serin

  3. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Vijay L. Manthati & John R. Falck

  4. Department of Pharmacology, College of Medicine, Center for Health Sciences, University of Tennessee, Memphis, TN, USA

    Kafait U. Malik

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  1. A. Nihal Sari
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Sari, A.N., Korkmaz, B., Serin, M.S. et al. Effects of 5,14-HEDGE, a 20-HETE mimetic, on lipopolysaccharide-induced changes in MyD88/TAK1/IKKβ/IκB-α/NF-κB pathway and circulating miR-150, miR-223, and miR-297 levels in a rat model of septic shock. Inflamm. Res. 63, 741–756 (2014). https://doi.org/10.1007/s00011-014-0747-z

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