Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells

Cell Communication and Signaling

Volumn 16, Issue 1, 2018, Pages

  Zegeye, Mulugeta M ^a   Lindkvist, Madelene ^a   Fälker, Knut ^a   Kumawat, Ashok K ^a   Paramel, Geena ^a,b   Grenegård, Magnus ^a   Sirsjö, Allan ^a   Ljungberg, Liza U ^a  

^a ÖREBRO UNIVERSITY   (Sweden)

^b DALHOUSIE UNIVERSITY   (Canada)

Author keywords

Endothelium; HUVECs; Interleukin 6 signaling; Monocyte chemoattractant Protein 1; Pro inflammatory cytokines

Indexed keywords

GLYCOPROTEIN GP 130; INTERLEUKIN 6; MONOCYTE CHEMOTACTIC PROTEIN 1; CCL2 PROTEIN, HUMAN; JANUS KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; STAT3 PROTEIN;

ARTICLE; CELL ACTIVATION; CONTROLLED STUDY; DOWN REGULATION; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNOBLOTTING; JAK-STAT SIGNALING; MAPK SIGNALING; PI3K/AKT SIGNALING; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; UPREGULATION; VASCULAR ENDOTHELIAL CELL; ENDOTHELIUM CELL; GENE EXPRESSION REGULATION; INFLAMMATION; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION; UMBILICAL VEIN ENDOTHELIAL CELL;

CHEMOKINE CCL2; ENDOTHELIAL CELLS; GENE EXPRESSION REGULATION; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; INFLAMMATION; INTERLEUKIN-6; JANUS KINASES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 85053157310     PISSN: None     EISSN: 1478811X     Source Type: Journal    
DOI: 10.1186/s12964-018-0268-4     Document Type: Article

References (38)

1. Gimbrone MA, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 2016;118:620-36. https://doi.org/10.1161/CIRCRESAHA.115.306301.
2. Ataie-Kachoie P, Pourgholami MH, Richardson DR, Morris DL. Gene of the month: interleukin 6 (IL-6). J Clin Pathol. 2014;67:932-7. https://doi.org/10.1136/jclinpath-2014-202493.
3. Suzuki M, Hashizume M, Yoshida H, Mihara M. Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: effect on the expression of chemokine and adhesion molecule. Rheumatol Int. 2010;30:309-15. https://doi.org/10.1007/s00296-009-0953-0.
4. Wung BS, Ni CW, Wang DL. ICAM-1 induction by TNFalpha and IL-6 is mediated by distinct pathways via Rac in endothelial cells. J Biomed Sci. 2005;12:91-101. https://doi.org/10.1007/s11373-004-8170-z.
5. Dawson TC, Kuziel WA, Osahar TA, Maeda N. Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis. 1999;143:205-11. https://doi.org/10.1016/S0021-9150(98)00318-9.
6. Öhman MK, Wright AP, Wickenheiser KJ, Luo W, Russo HM, Eitzman DT. Monocyte chemoattractant protein-1 deficiency protects against visceral fat-induced atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30:1151-8. https://doi.org/10.1161/ATVBAHA.110.205914.
7. Zhang X, Liu X, Shang H, Xu Y, Qian M. Monocyte chemoattractant protein-1 induces endothelial cell apoptosis in vitro through a p53-dependent mitochondrial pathway. Acta Biochim Biophys Sin. 2011;43:787-95. https://doi.org/10.1093/abbs/gmr072.Advance.
8. Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, et al. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther. 2014;141:125-9. https://doi.org/10.1016/j.pharmthera.2013.09.004.
9. Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci. 2012;8:1227-36. https://doi.org/10.7150/ijbs.4666.
10. Md Yusof MY, Emery P. Targeting interleukin-6 in rheumatoid arthritis. Drugs. 2013;73:341-56. https://doi.org/10.1007/s40265-013-0018-2.
11. Schiff MH, Kremer JM, Jahreis A, Vernon E, Isaacs JD, van Vollenhoven RF. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011;13:R141. https://doi.org/10.1186/ar3455.
12. Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei X-F, et al. IL-6 is an Antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest. 1998;101:311-20. https://doi.org/10.1172/JCI1368.
13. Madan M, Bishayi B, Hoge M, Amar S. Atheroprotective role of interleukin-6 in diet- and/or pathogen-associated atherosclerosis using an ApoE heterozygote murine model. Atherosclerosis. 2008;197:504-14. https://doi.org/10.1016/j.atherosclerosis.2007.02.023.
14. Leibinger M, Müller A, Gobrecht P, Diekmann H, Andreadaki A, Fischer D. Interleukin-6 contributes to CNS axon regeneration upon inflammatory stimulation. Cell Death Dis. 2013;4 https://doi.org/10.1038/cddis.2013.126.
15. Schaper F, Rose-John S. Interleukin-6: biology, signaling and strategies of blockade. Cytokine Growth Factor Rev. 2015;26:475-87. https://doi.org/10.1016/j.cytogfr.2015.07.004.
16. Wolf J, Rose-John S, Garbers C. Interleukin-6 and its receptors: a highly regulated and dynamic system. Cytokine. 2014;70:11-20. https://doi.org/10.1016/j.cyto.2014.05.024.
17. Schumacher N, Meyer D, Mauermann A, Von Der Heyde J, Wolf J, Schwarz J, et al. Shedding of endogenous interleukin-6 receptor (IL-6R) is governed by a disintegrin and metalloproteinase (ADAM) proteases while a full-length IL-6R isoform localizes to circulating microvesicles. J Biol Chem. 2015;290:26059-71. https://doi.org/10.1074/jbc.M115.649509.
18. Riethmueller S, Somasundaram P, Ehlers JC, Hung CW, Flynn CM, Lokau J, et al. Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation. PLOS Biology. 2017;15. https://doi.org/10.1371/journal.pbio.2000080.
19. Rose-John S. Il-6 trans-signaling via the soluble IL-6 receptor: importance for the proinflammatory activities of IL-6. Int J Biol Sci. 2012;8:1237-47. https://doi.org/10.7150/ijbs.4989.
20. Jones SA, Rose-John S. The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R/IL-6 complex. Biochim Biophys Acta, Mol Cell Res. 2002;1592:251-63. https://doi.org/10.1016/S0167-4889(02)00319-1.
21. Reiss AB, Siegart NM, De Leon J. Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clin Lipidol. 2017;12:14-23. https://doi.org/10.1080/17584299.2017.1319787.
22. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta, Mol Cell Res. 2011;1813:878-88. https://doi.org/10.1016/j.bbamcr.2011.01.034.
23. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6:315-25. https://doi.org/10.1016/S1074-7613(00)80334-9.
24. Chatterjee PK, Al-Abed Y, Sherry B, Metz CN. Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell activation. Am J Physiol Physiol. 2009;297:C1294-306. https://doi.org/10.1152/ajpcell.00160.2009.
25. Sanceau J, Wijdenes J, Revel M, Wietzerbin J. IL-6 and IL-6 receptor modulation by IFN-gamma and tumor necrosis factor-alpha in human monocytic cell line (THP-1). Priming effect of IFN-gamma. J Immunol. 1991;147:2630-7.
26. Bauer J, Lengyel G, Bauer TM, Acs G, Gerok W. Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes. FEBS Lett. 1989;249:27-30. https://doi.org/10.1016/0014-5793(89)80008-0.
27. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, et al. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988;241:825-8. https://doi.org/10.1126/science.3136546.
28. HEINRICH PC, BEHRMANN I, MÜLLER-NEWEN G, SCHAPER F, GRAEVE L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998;334:297-314. https://doi.org/10.1042/bj3340297.
29. Eulenfeld R, Dittrich A, Khouri C, Müller PJ, Mütze B, Wolf A, et al. Interleukin-6 signalling: more than Jaks and STATs. Eur J Cell Biol. 2012;91:486-95. https://doi.org/10.1016/j.ejcb.2011.09.010.
30. Lang R, Pauleau AL, Parganas E, Takahashi Y, Mages J, Ihle JN, et al. SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol. 2003;4:546-50. https://doi.org/10.1038/ni932.
31. Martin T, Cardarelli PM, Parry GC, Felts KA, Cobb RR. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1. Eur J Immunol. 1997;27:1091-7. https://doi.org/10.1002/eji.1830270508.
32. Wang L, Walia B, Evans J, Gewirtz AT, Merlin D, Sitaraman SV. IL-6 induces NF- B activation in the intestinal epithelia. J Immunol. 2003;171:3194-201. https://doi.org/10.4049/jimmunol.171.6.3194.
33. Kiu H, Nicholson SE. Biology and significance of the JAK/STAT signalling pathways. Growth Factors. 2012;30:88-106. https://doi.org/10.3109/08977194.2012.660936.
34. Saleiro D, Platanias LC. Intersection of mTOR and STAT signaling in immunity. Trends Immunol. 2015;36:21-9. https://doi.org/10.1016/j.it.2014.10.006.
35. Yokogami K, Wakisaka S, Avruch J, Reeves SA. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr Biol. 2000;10:47-50. https://doi.org/10.1016/S0960-9822(99)00268-7.
36. Kim JH, Jae EK, Liu HY, Cao W, Chen J. Regulation of interleukin-6-induced hepatic insulin resistance by mammalian target of rapamycin through the STAT3-SOCS3 pathway. J Biol Chem. 2008;283:708-15. https://doi.org/10.1074/jbc.M708568200.
37. Kim J-H, Yoon M-S, Chen J. Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. J Biol Chem. 2009;284:35425-32. https://doi.org/10.1074/jbc.M109.051516.
38. Sobota RM, Müller PJ, Heinrich PC, Schaper F. Prostaglandin E1 inhibits IL-6-induced MCP-1 expression by interfering specifically in IL-6-dependent ERK1/2, but not STAT3, activation. Biochem J. 2008;412:65-72. https://doi.org/10.1042/BJ20071572.