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Kynurenic acid downregulates IL-17/1L-23 axis in vitro

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Abstract

Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC’s) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production. In this study, we sought to explore the potential role of kynurenic acid (KynA), in modulating the expression of IL-23 and IL-17 by DCs and CD4+ cells, respectively. The result of flow cytometry demonstrated that the frequency of IL-23-producing DCs is reduced with 100 µg/ml of KynA as compared with that of LPS-stimulated DCs. KynA (100 μg/ml) addition to activated T cells significantly decreased the level of IL-17 mRNA and frequency of IL-17+ T cells as compared to that of concanavalin (Con) A-activated T cells. To examine the mechanism of the suppressive role of KynA on IL-23/IL-17 in these cells, cells were treated with 3 μM G-protein-coupled receptor35 (GPCR35) inhibitor (CID), for 60 min. The result showed that the reduction of both adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) by KynA is involved in suppression of LPS-induced IL-23p19 expression. Since GPCR35 is also detected on T cells; therefore, it is concluded that KynA plays an important role in modulating the expression of IL-23 and IL-17 in DCs and Th17 cells through inhibiting GPCR35 and downregulation of both AC and cAMP.

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References

  1. Neill L, Tien AH, Rey-Ladino J, Helgason CD (2007) SHIP-deficient mice provide insights into the regulation of dendritic cell development and function. Exp Hematol 35:627–639. doi:10.1016/j.exphem.2007.01.048

    Article  CAS  PubMed  Google Scholar 

  2. Germain RN (1994) MHC-dependent antigen processing and peptide presentation: providing ligans for T lymphocyte activation. Cell 76:287–299

    Article  CAS  PubMed  Google Scholar 

  3. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252. doi:10.1038/32588

    Article  CAS  PubMed  Google Scholar 

  4. Liu Y, Janeway CA (1992) Cells that present both specific ligand and costimulatory activity are the most efficient inducers of clonal expansion of normal CD4 T cells. Proc Natl Acad Sci USA 89:3845–3849. doi:10.1073/pnas.89.9.3845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Spoerri R, Reis e Sousa C, Nolte M, Joffre O (2009) Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunol Rev 227:234–247. doi:10.1111/j.1600-065X.2008.00718.x

    Article  Google Scholar 

  6. Zhu J, Paul WE (2010) Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev 238:247–262. doi:10.1111/j.1600-065X.2010.00951.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lanzavecchia A, Sallusto F (2010) Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science 290:92–97. doi:10.1126/science.290.5489.92

    Article  Google Scholar 

  8. Awasthi A, Riol-Blanco L, Jäger A, Korn T, Pot C, Galileos G, Bettelli E, Kuchroo VK, Oukka M (2009) Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells. J Immunol 182:5904–5908. doi:10.4049/jimmunol.0900732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kyttaris VC, Zhang Z, Kuchroo VK, Oukka M, Tsokos GC (2010) Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol 184:4605–4609. doi:10.1016/j.ymed.2011.09.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, McClanahan TK, O’Shea JJ, Cua DJ (2009) The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 10:314–324. doi: 10.1038/ni.1698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kolls JK, Lindén A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476. doi:10.1016/j.immuni.2004.08.018

    Article  CAS  PubMed  Google Scholar 

  12. Maddur MS, Miossec P, Kaveri SV, Bayry J (2012) Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 181:8–18. doi:10.1016/j.ajpath.2012.03.044

    Article  CAS  PubMed  Google Scholar 

  13. Shen H, Goodall JC, Hill Gaston JS (2009) Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 60:1647–1656. doi:10.1002/art.24568

    Article  CAS  PubMed  Google Scholar 

  14. Lubberts E, Koenders MI, van den Berg WB (2005) The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res Ther 7:29–37. doi:10.1186/ar1478

    Article  CAS  PubMed  Google Scholar 

  15. Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X, Wan L, Li M (2009) Th17 and natural treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum 60:1472–1483. doi:10.1002/art.24499

    Article  PubMed  Google Scholar 

  16. Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont M-C, Ranchin B, Fabien N, Cochat P, Pouteil-Noble C, Trolliet P, Durieu I, Tebib J, Kassai B, Ansieau S, Puisieux A, Eliaou J-F, Bonnefoy-Bérard N (2009) Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol 10:778–785. doi:10.1038/ni.1741

    Article  CAS  PubMed  Google Scholar 

  17. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172:146–155. doi:10.2353/ajpath.2008.070690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, Bowman EP, Krueger JG (2008) Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 128:1207–1211. doi:10.1038/sj.jid.5701213

    Article  CAS  PubMed  Google Scholar 

  19. Malakouti M, Brown GE, Wang E, Koo J, Levin EC (2014) The role of IL-17 in psoriasis. J Dermatolog Treat 6634:1–4. doi:10.3109/09546634.2013.879093

    Google Scholar 

  20. Zenewicz LA, Antov A, Flavell RA (2009) CD4 T-cell differentiation and inflammatory bowel disease. Trends Mol Med 15:199–207. doi:10.1016/j.molmed.2009.03.002

    Article  CAS  PubMed  Google Scholar 

  21. Wilke CM, Bishop K, Fox D, Zou W (2011) Deciphering the role of Th17 cells in human disease. Trends Immunol 32:603–611. doi:10.1016/j.it.2011.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cosmi L, Maggi L, Santarlasci V, Capone M, Cardilicchia E, Frosali F, Querci V, Angeli R, Matucci A, Fambrini M, Liotta F, Parronchi P, Maggi E, Romagnani S, Annunziato F (2010) Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4. J Allergy Clin Immunol 125(222–230):e4. doi:10.1016/j.jaci.2009.10.012

    Google Scholar 

  23. Costa VS, Mattana TCC, da Silva MER (2010) Unregulated IL-23/IL-17 immune response in autoimmune diseases. Diabetes Res Clin Pract 88:222–226. doi:10.1016/j.diabres.2010.03.014

    Article  CAS  PubMed  Google Scholar 

  24. Kikly K, Liu L, Na S, Sedgwick JD (2006) The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18:670–675. doi:10.1016/j.coi.2006.09.008

    Article  CAS  PubMed  Google Scholar 

  25. Hazlett J, Stamp, LK, Merriman T, Highton J, Hessian P (2011) IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis. Genes Immun 13:282–287. doi:10.1038/gene.2011.80

    Article  PubMed  Google Scholar 

  26. Mok MY, Wu HJ, Lo Y, Lau CS (2010) The relation of interleukin 17 (IL-17) and IL-23 to Th1/Th2 cytokines and disease activity in systemic lupus erythematosus. J Rheumatol 37:2046–2052. doi:10.3899/jrheum.100293

    Article  PubMed  Google Scholar 

  27. Shen H, Xia L, Lu J, Xiao W (2011) Interleukin-17 and interleukin-23 in patients with polymyositis and dermatomyositis. Scand J Rheumatol 40:217–220. doi:10.3109/03009742.2010.517215

    Article  CAS  PubMed  Google Scholar 

  28. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240. doi:10.1084/jem.20041257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nakajima K, Kanda T, Takaishi M, Shiga T, Miyoshi K, Nakajima H, Kamijima R, Tarutani M, Benson JM, Elloso MM, Gutshall LL, Naso MF, Iwakura Y, DiGiovanni J, Sano S (2011) Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. J Immunol 186:4481–4489. doi:10.4049/jimmunol.1000148

    Article  CAS  PubMed  Google Scholar 

  30. D’Elios MM, Del Prete G, Amedei A (2010) Targeting IL-23 in human diseases. Expert Opin Ther Targets 14:759–774. doi:10.1517/14728222.2010.497143

    Article  PubMed  Google Scholar 

  31. Kurzeja M, Rudnicka L, Olszewska M (2011) New interleukin-23 pathway inhibitors in dermatology: ustekinumab, briakinumab, and secukinumab. Am J Clin Dermatol 12:113–125. doi:10.2165/11538950-000000000-00000

    Article  PubMed  Google Scholar 

  32. Genovese MC, Van Den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, Sloan-Lancaster J (2010) LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 62:929–939. doi:10.1002/art.27334

    Article  CAS  PubMed  Google Scholar 

  33. Patel RV, Clark LN, Lebwohl M, Weinberg JM (2009) Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol 60:1001–1017. doi:10.1016/j.jaad.2008.12.031

    Article  PubMed  Google Scholar 

  34. Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL, Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191–1193. doi:10.1126/science.281.5380.1191

    Article  CAS  PubMed  Google Scholar 

  35. Mándi Y, Vécsei L (2012) The kynurenine system and immunoregulation. J Neural Transm 119:197–209. doi:10.1007/s00702-011-0681-y

    Article  PubMed  Google Scholar 

  36. Kudo Y, Boyd CAR, Sargent IL, Redman CWG (2001) Tryptophan degradation by human placental indoleamine 2, 3-dioxygenase regulates lymphocyte proliferation. J Physiol 535:207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor a L (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189:1363–1372. doi:10.1084/jem.189.9.1363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Curran TA, Jalili RB, Farrokhi A, Ghahary A (2014) IDO expressing fibroblasts promote the expansion of antigen specific regulatory T cells. Immunobiology 219:17–24. doi:10.1016/j.imbio.2013.06.008

    Article  CAS  PubMed  Google Scholar 

  39. Forouzandeh F, Jalili RB, Hartwell RV, Allan SE, Boyce S, Supp D, Ghahary A (2010) Local expression of indoleamine 2,3-dioxygenase suppresses T-cell-mediated rejection of an engineered bilayer skin substitute. Wound Repair Regen 18:614–623. doi:10.1111/j.1524-475X.2010.00635.x

    Article  PubMed  Google Scholar 

  40. Poormasjedi-Meibod MS, Jalili RB, Hosseini-Tabatabaei A, Hartwell R, Ghahary A (2013) Immuno-regulatory function of indoleamine 2,3 dioxygenase through modulation of innate immune responses. PLoS ONE. doi:10.1371/journal.pone.0071044

    PubMed  PubMed Central  Google Scholar 

  41. Moffett JR, Namboodiri MA (2003) Tryptophan and the immune response. Immunol Cell Biol 81:247–265. doi:10.1046/j.1440-1711.2003.t01-1-01177.x

    Article  CAS  PubMed  Google Scholar 

  42. Małaczewska J, Siwicki AK, Wójcik RM, Kaczorek E, Turski WA (2014) Effect of oral administration of kynurenic acid on the activity of the peripheral blood leukocytes in mice. Cent Eur J Immunol 1:6–13. doi:10.5114/ceji.2014.42115

    Article  Google Scholar 

  43. Csáti A, Edvinsson L, Vécsei L, Toldi J, Fülöp F, Tajti J, Warfvinge K (2015) Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion. J Headache Pain 16:99. doi:10.1186/s10194-015-0581-x

    Article  PubMed  PubMed Central  Google Scholar 

  44. Fallarini S, Magliulo L, Paoletti T, de Lalla C, Lombardi G (2010) Expression of functional GPR35 in human iNKT cells. Biochem Biophys Res Commun 398:420–425. doi:10.1016/j.bbrc.2010.06.091

    Article  CAS  PubMed  Google Scholar 

  45. Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L (2006) Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem 281:22021–22028. doi:10.1074/jbc.M603503200

    Article  CAS  PubMed  Google Scholar 

  46. Moroni F, Fossati S, Chiarugi A, Cozzi A (2007) Kynurenic acid actions in brain and periphery. Int Congr Ser 1304:305–313. doi:10.1016/j.ics.2007.07.016

    Article  CAS  Google Scholar 

  47. Shi Q, Yin Z, Zhao B, Sun F, Yu H, Yin X, Zhang L, Wang S (2015) PGE2 elevates IL-23 production in human dendritic cells via a cAMP dependent pathway. Mediators Inflamm 2015:1–8

    Google Scholar 

  48. Lutz MB, Kukutsch N, Ogilvie a L, Rössner S, Koch F, Romani N, Schuler G (1999) An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods 223:77–92. doi:10.1016/S0022-1759(98)00204-X

    Article  CAS  PubMed  Google Scholar 

  49. Sanam SE, Malihe-Sadat P-M, Yunyuan L, Reza B. J, Aziz G (2014) Effects of kynurenine on CD3+ and macrophages in wound healing. Wound Repair Regen 23:90–97. doi:10.1111/wrr.12252

    Google Scholar 

  50. Roses RE, Xu S, Xu M, Koldovsky U, Koski G, Czerniecki BJ (2008) Differential production of IL-23 and IL-12 by myeloid-derived dendritic cells in response to TLR agonists. J Immunol 181:5120–5127. doi:10.4049/jimmunol.181.7.5120

    Article  CAS  PubMed  Google Scholar 

  51. Kambayashi T, Wallin RP, Ljunggren HG (2001) cAMP-elevating agents suppress dendritic cell function. J Leukoc Biol 70:903–910

    CAS  PubMed  Google Scholar 

  52. Chang J, Voorhees TJ, Liu Y, Zhao Y, Chang C-H (2010) Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A. Proc Natl Acad Sci USA 107:8340–8345. doi:10.1073/pnas.0914703107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Abdi K, Singh NJ, Matzinger P (2012) Lipopolysaccharide-activated dendritic cells: “exhausted” or alert and waiting? J Immunol 188:5981–5989. doi:10.4049/jimmunol.1102868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Aggarwal S, Ghilardi N, Xie MH, De Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278:1910–1914. doi:10.1074/jbc.M207577200

    Article  CAS  PubMed  Google Scholar 

  55. Cozzi A, Attucci S, Peruginelli F, Marinozzi M, Luneia R, Pellicciari R, Moroni F (1997) Type 2 metabotropic glutamate (mGlu) receptors tonically inhibit transmitter release in rat caudate nucleus: in vivo studies with (2S,1′S,2′S,3′R)-2-(2′-carboxy-3′-phenylcyclopropyl)glycine, a new potent and selective antagonist. Eur J Neurosci 9:1350–1355

    Article  CAS  PubMed  Google Scholar 

  56. Lombardi G, Alesiani M, Leonardi P, Cherici G, Pellicciari R, Moroni F (1993) Pharmacological characterization of the metabotropic glutamate receptor inhibiting D-[3H]-aspartate output in rat striatum. Br J Pharmacol 110:1407–1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. McKenzie BS, Kastelein RA, Cua DJ (2006) Understanding the IL-23–IL-17 immune pathway. Trends Immunol 27:17–23. doi:10.1016/j.it.2005.10.003

    Article  CAS  PubMed  Google Scholar 

  58. Gleick PH, MacDonald GM (2010) Roadmap for sustainable water resources in southwestern North America. Proc Natl Acad Sci USA 107:21300–21305. doi:10.1073/pnas

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Carlson T, Kroenke M, Rao P, Lane TE, Segal B (2008) The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. J Exp Med 205:811–823. doi:10.1084/jem.20072404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu B-M, Tato C, Yoshimura A, Hennighausen L, O’Shea JJ (2006) Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA 103:8137–8142. doi:10.1073/pnas.0600666103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kaszaki J, Palásthy Z, Erczes D, Rácz A, Torday C, Varga G, Vécsei L, Boros M (2008) Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs. Neurogastroenterol Motil 20:53–62. doi:10.1111/j.1365-2982.2007.00989.x

    CAS  PubMed  Google Scholar 

  62. Varga G, Erces D, Fazekas B, Fülöp M, Kovács T, Kaszaki J, Fülöp F, Vécsei L, Boros M (2010) N-Methyl-D-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat. Neurogastroenterol Motil 22(217–25):e68. doi:10.1111/j.1365-2982.2009.01390.x

    Google Scholar 

  63. Tiszlavicz Z, Németh B, Fülöp F, Vécsei L, Tápai K, Ocsovszky I, Mándi Y (2011) Different inhibitory effects of kynurenic acid and a novel kynurenic acid analogue on tumour necrosis factor-α (TNF-α) production by mononuclear cells, HMGB1 production by monocytes and HNP1-3 secretion by neutrophils. Naunyn Schmiedeberg’s Arch Pharmacol 383:447–455. doi:10.1007/s00210-011-0605-2

    Article  CAS  Google Scholar 

  64. Badawy AA-B (2015) Tryptophan metabolism, disposition and utilization in pregnancy. Biosci Rep 35:e00261–e00261. doi:10.1042/BSR20150197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Roberts DJ, Waelbroeck M (2004) G protein activation by G protein coupled receptors: ternary complex formation or catalyzed reaction? Biochem Pharmacol 68:799–806. doi:10.1016/j.bcp.2004.05.044

    Article  CAS  PubMed  Google Scholar 

  66. Preininger AM, Hamm HE (2010) G protein signaling: insights from new structures. Sci STKE 2004:1–10. doi:10.1126/stke.2182004re3

    Google Scholar 

  67. Birnbaumer L (2007) Expansion of signal transduction by G proteins. Biochim Biophys Acta 1768:772–793. doi:10.1016/j.bbamem.2006.12.002

    Article  CAS  PubMed  Google Scholar 

  68. Liu W, Ouyang X, Yang J, Liu J, Li Q, Gu Y, Fukata M, Lin T, He JC, Abreu M, Unkeless JC, Meyer L, Xiong H (2009) AP-1 activated by toll-like receptors regulates expression of IL-23 p19. J Biol Chem 284:24006–24016. doi:10.1074/jbc.M109.025528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Uh A, Simmons CF, Bresee C, Khoury N, Gombart AF, Nicholson RC, Kocak H, Equils O (2009) MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line. Reprod Biol Endocrinol 7:74. doi:10.1186/1477-7827-7-74

    Article  PubMed  PubMed Central  Google Scholar 

  70. Zhao P, Sharir H, Kapur A, Cowan A, Geller EB, Adler MW, Seltzman HH, Reggio PH, Heynen-Genel S, Sauer M, Chung TDY, Bai Y, Chen W, Caron MG, Barak LS, Abood ME (2010) Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of extracellular signal-regulated kinase and β-arrestin2 with antinociceptive activity. Mol Pharmacol 78:560–568. doi:10.1124/mol.110.066746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study has been supported by POP grant (CIHR PPP-133379). Sanam Salimi Elizei is supported by a WorkSafe BC Research Training Award. We would like to thank Dr. Ryan Hartwell for his kindness in editing the final version of the manuscript.

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Authors and Affiliations

  1. BC Professional Firefighters’ Burn & Wound Healing Research Laboratory, Department of Surgery, University of British Columbia, 4550 ICORD, 818 10th Avenue West, Vancouver, BC, V5Z 1M9, Canada

    Sanam Salimi Elizei, Maryam Kheirandish & Aziz Ghahary

  2. International Collaboration on Repair Discoveries, School of Kinesiology, University of British Columbia, Vancouver, BC, Canada

    Malihe-Sadat Poormasjedi-Meibod

  3. The Developmental Neurobiology Research Laboratory, Department of Ophthalmology and Visual Science, University of British Columbia, Vancouver, BC, Canada

    Xia Wang

  4. Blood Transfusion Research Center, High Institute for Research and Education, Tehran, Iran

    Maryam Kheirandish

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  1. Sanam Salimi Elizei
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Salimi Elizei, S., Poormasjedi-Meibod, MS., Wang, X. et al. Kynurenic acid downregulates IL-17/1L-23 axis in vitro. Mol Cell Biochem 431, 55–65 (2017). https://doi.org/10.1007/s11010-017-2975-3

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