Skip to main content

Advertisement

SpringerLink
Log in

JNJ7777120 Ameliorates Inflammatory and Oxidative Manifestations in a Murine Model of Contact Hypersensitivity via Modulation of TLR and Nrf2 Signaling

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

JNJ7777120, a histamine H4 receptor antagonist, was shown to be effective in different experimental settings of allergic inflammation, including contact hypersensitivity. Toll-like receptors (TLRs) are thought to function as a link between innate and adaptive immune responses to various haptens. Here, we studied the suppression of TLR signaling as a possible mechanism by which JNJ7777120 exerts its anti-inflammatory effects against the chemical hapten, fluorescein isothiocyanate (FITC). The potential anti-oxidant effect of JNJ7777120 in this model was also examined. Mice subjected to FITC sensitization and challenge showed significantly elevated plasma immunoglobulin E (IgE) level, ear interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid reactive substance (TBARS) contents as well as increased myeloid differentiation factor 88 (MyD88) gene expression, nuclear factor-kappa B p65 (NF-κB p65), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) protein expression. This was accompanied by enhanced ear myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities as well as diminished glutathione (GSH) content and superoxide dismutase (SOD) activity. JNJ7777120 treatment perceivably reversed these effects, denoting profound anti-inflammatory and anti-oxidant character of JNJ7777120 which was confirmed by its mitigation of FITC-induced pathological changes in mouse ear. JNJ7777120 additionally enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), providing a novel mechanism by which JNJ7777120 functions as an anti-oxidant in this model. To conclude, JNJ7777120 afforded a remarkable amendment of FITC skin insult by virtue of its anti-inflammatory and anti-oxidant effects; the mechanistic basis of these effects may include modulation of TLR and Nrf2 pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Watanabe, Hideaki, Mark Unger, Brandon Tuvel, Binghe Wang, and Daniel N. Sauder. 2002. Contact hypersensitivity: the mechanism of immune responses and T cell balance. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 22: 407–412. https://doi.org/10.1089/10799900252952181.

    Article  CAS  Google Scholar 

  2. Corsini, Emanuela, Valentina Galbiati, Dragana Nikitovic, and Aristidis M. Tsatsakis. 2013. Role of oxidative stress in chemical allergens induced skin cells activation. Food and Chemical Toxicology 61. Elsevier Ltd: 74–81. https://doi.org/10.1016/j.fct.2013.02.038.

    Article  CAS  PubMed  Google Scholar 

  3. Kaplan, Daniel H., Botond Z. Igyártó, and Anthony A. Gaspari. 2012. Early immune events in the induction of allergic contact dermatitis. Nature Reviews Immunology 12. Nature Publishing Group: 114–124. https://doi.org/10.1038/nri3150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tang, A., T.A. Judge, B.J. Nickoloff, and L.A. Turka. 1996. Suppression of murine allergic contact dermatitis by CTLA4Ig. Tolerance induction of Th2 responses requires additional blockade of CD40-ligand. Journal of Immunology (Baltimore, Md. : 1950) 157: 117–125.

    CAS  Google Scholar 

  5. Takeshita, Keisuke, Tsugiko Yamasaki, Shizuo Akira, Florian Gantner, and Kevin B. Bacon. 2004. Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse. International Immunology 16: 685–695. https://doi.org/10.1093/intimm/dxh073.

    Article  CAS  PubMed  Google Scholar 

  6. Trinchieri, Giorgio, and Alan Sher. 2007. Cooperation of Toll-like receptor signals in innate immune defence. Nature Reviews. Immunology 7: 179–190. https://doi.org/10.1038/nri2038.

    Article  CAS  PubMed  Google Scholar 

  7. Sloane, Jacob A., Daina Blitz, Zachary Margolin, and Timothy Vartanian. 2010. A clear and present danger: endogenous ligands of Toll-like receptors. Neuromolecular Medicine 12: 149–163. https://doi.org/10.1007/s12017-009-8094-x.

    Article  CAS  PubMed  Google Scholar 

  8. Akira, Shizuo, and Kiyoshi Takeda. 2004. Toll-like receptor signalling. Nature Reviews. Immunology 4: 499–511. https://doi.org/10.1038/nri1391.

    Article  CAS  PubMed  Google Scholar 

  9. Miller, Lloyd S. 2008. Toll-like receptors in skin. Advances in Dermatology 24: 71–87. https://doi.org/10.1016/j.yadr.2008.09.004.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Martin, Stefan F., Jan C. Dudda, Eva Bachtanian, Annalisa Lembo, Stefanie Liller, Christoph Dürr, Markus M. Heimesaat, et al. 2008. Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. The Journal of Experimental Medicine 205: 2151–2162. https://doi.org/10.1084/jem.20070509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Korkina, Liudmila, and Saveria Pastore. 2009. The role of redox regulation in the normal physiology and inflammatory diseases of skin. Frontiers in Bioscience (Elite Edition) 1: 123–141.

    Google Scholar 

  12. Kobayashi, Makoto, and Masayuki Yamamoto. 2006. Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Advances in Enzyme Regulation 46: 113–140. https://doi.org/10.1016/j.advenzreg.2006.01.007.

    Article  CAS  PubMed  Google Scholar 

  13. Dunford, Paul J., Niall O’Donnell, Jason P. Riley, Kacy N. Williams, Lars Karlsson, and Robin L. Thurmond. 2006. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. Journal of Immunology (Baltimore, Md. : 1950) 176: 7062–7070. https://doi.org/10.4049/jimmunol.176.11.7062.

    Article  CAS  Google Scholar 

  14. Cowden, Jeffery M., Mai Zhang, Paul J. Dunford, and Robin L. Thurmond. 2010. The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. The Journal of Investigative Dermatology 130. Nature Publishing Group: 1023–1033. https://doi.org/10.1038/jid.2009.358.

    Article  CAS  PubMed  Google Scholar 

  15. Ling, Ping, Karen Ngo, Steven Nguyen, Robin L. Thurmond, James P. Edwards, Lars Karlsson, and Wai-Ping Fung-Leung. 2004. Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. British Journal of Pharmacology 142: 161–171. https://doi.org/10.1038/sj.bjp.0705729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hofstra, Claudia L., Pragnya J. Desai, Robin L. Thurmond, and Wai Ping Fung-Leung. 2003. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. Journal of Pharmacology and Experimental Therapeutics 305: 1212–1221. https://doi.org/10.1124/jpet.102.046581.

    Article  CAS  PubMed  Google Scholar 

  17. Bäumer, W., S. Wendorff, R. Gutzmer, T. Werfel, D. Dijkstra, P. Chazot, H. Stark, and M. Kietzmann. 2008. Histamine H4 receptors modulate dendritic cell migration through skin—immunomodulatory role of histamine. Allergy: European Journal of Allergy and Clinical Immunology 63: 1387–1394. https://doi.org/10.1111/j.1398-9995.2008.01720.x.

    Article  PubMed  Google Scholar 

  18. Gutzmer, R., C. Diestel, S. Mommert, B. Kother, H. Stark, M. Wittmann, and T. Werfel. 2005. Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. The Journal of Immunology 174: 5224–5232. https://doi.org/10.4049/jimmunol.174.9.5224.

    Article  CAS  PubMed  Google Scholar 

  19. Gutzmer, Ralf, Susanne Mommert, Maria Gschwandtner, Katja Zwingmann, Holger Stark, and Thomas Werfel. 2009. The histamine H4 receptor is functionally expressed on TH2 cells. Journal of Allergy and Clinical Immunology 123: 619–625. https://doi.org/10.1016/j.jaci.2008.12.1110.

    Article  CAS  PubMed  Google Scholar 

  20. Desai, Pragnya, and Robin L. Thurmond. 2011. Histamine H4 receptor activation enhances LPS-induced IL-6 production in mast cells via ERK and PI3K activation. European Journal of Immunology 41: 1764–1773. https://doi.org/10.1002/eji.201040932.

    Article  CAS  PubMed  Google Scholar 

  21. Cowden, Jeffery M., Yu Fuqu, Mamatha Challapalli, Jing Feng Huang, Sunhwa Kim, Wai Ping Fung-Leung, Jing Ying Ma, et al. 2013. Antagonism of the histamine H4 receptor reduces LPS-induced TNF production in vivo. Inflammation Research 62: 599–607. https://doi.org/10.1007/s00011-013-0612-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Boehme, Stefen A., Karin Franz-Bacon, Edward P. Chen, Roman Šášik, L. James Sprague, Tai Wei Ly, Gary Hardiman, et al. 2009. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. International Immunology 21: 81–93. https://doi.org/10.1093/intimm/dxn127.

    Article  CAS  PubMed  Google Scholar 

  23. Dunford, Paul J., Kacy N. Williams, Pragnya J. Desai, Lars Karlsson, Daniel McQueen, and Robin L. Thurmond. 2007. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. The Journal of Allergy and Clinical Immunology 119: 176–183. https://doi.org/10.1016/j.jaci.2006.08.034.

    Article  CAS  PubMed  Google Scholar 

  24. Beutler, Ernest, Olga Duron, and Barbara Mikus Kelly. 1963. Improved method for the determination of blood glutathione. The Journal of Laboratory and Clinical Medicine 61: 882–888.

    CAS  PubMed  Google Scholar 

  25. Uchiyama, Mitsuru, and Midori Mihara. 1978. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytical Biochemistry 86: 271–278. https://doi.org/10.1016/0003-2697(78)90342-1.

    Article  CAS  PubMed  Google Scholar 

  26. Marklund, S., and G. Marklund. 1974. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry 47: 469–474.

    Article  CAS  PubMed  Google Scholar 

  27. Miranda, Katrina M., Michael G. Espey, and David A. Wink. 2001. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5: 62–71. https://doi.org/10.1006/niox.2000.0319.

    Article  CAS  PubMed  Google Scholar 

  28. Bradley, P.P., R.D. Christensen, and G. Rothstein. 1982. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 60: 618–622.

    CAS  PubMed  Google Scholar 

  29. Livak, Kenneth J., and Thomas D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25: 402–408. https://doi.org/10.1006/meth.2001.1262.

    Article  CAS  PubMed  Google Scholar 

  30. Roberts, David W., and Aynur O. Aptula. 2008. Determinants of skin sensitisation potential. Journal of Applied Toxicology 28: 377–387. https://doi.org/10.1002/jat.1289.

    Article  CAS  PubMed  Google Scholar 

  31. Martin, Stefan F. 2004. T lymphocyte-mediated immune responses to chemical haptens and metal ions: implications for allergic and autoimmune disease. International Archives of Allergy and Immunology 134: 186–198. https://doi.org/10.1159/000078765.

    Article  CAS  PubMed  Google Scholar 

  32. Larson, Ryan P., Simone C. Zimmerli, Michael R. Comeau, Andrea Itano, Miyuki Omori, Masanori Iseki, Conrad Hauser, and Steven F. Ziegler. 2010. Dibutyl phthalate-induced thymic stromal lymphopoietin is required for Th2 contact hypersensitivity responses. Journal of Immunology (Baltimore, Md. : 1950) 184: 2974–2984. https://doi.org/10.4049/jimmunol.0803478.

    Article  CAS  Google Scholar 

  33. Horr, Bianca, Hannelore Borck, Robin Thurmond, Sabine Grösch, and Friedhelm Diel. 2006. STAT1 phosphorylation and cleavage is regulated by the histamine (H4) receptor in human atopic and non-atopic lymphocytes. International Immunopharmacology 6: 1577–1585. https://doi.org/10.1016/j.intimp.2006.06.005.

    Article  CAS  PubMed  Google Scholar 

  34. Ohsawa, Yusuke, and Noriyasu Hirasawa. 2014. The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. Allergology international: official journal of the Japanese Society of Allergology 63: 533–542. https://doi.org/10.2332/allergolint.13-RA-0675.

    Article  CAS  Google Scholar 

  35. Akira, Shizuo, Satoshi Uematsu, and Osamu Takeuchi. 2006. Pathogen recognition and innate immunity. Cell 124: 783–801. https://doi.org/10.1016/j.cell.2006.02.015.

    Article  CAS  PubMed  Google Scholar 

  36. Chang, L., and M. Karin. 2001. Mammalian MAP kinase signalling cascades. Nature 410: 37–40. https://doi.org/10.1038/35065000.

    Article  CAS  PubMed  Google Scholar 

  37. Termeer, Christian, Frauke Benedix, Jonathon Sleeman, Christina Fieber, Ursula Voith, Thomas Ahrens, Kensuke Miyake, Marina Freudenberg, Christopher Galanos, and Jan Christoph Simon. 2002. Oligosaccharides of hyaluronan activate dendritic cells via Toll-like receptor 4. The Journal of Experimental Medicine 195: 99–111. https://doi.org/10.1084/jem.20001858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Scheibner, K.A., M.A. Lutz, S. Boodoo, M.J. Fenton, J.D. Powell, and M.R. Horton. 2006. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. The Journal of Immunology 177: 1272–1281. https://doi.org/10.4049/jimmunol.177.2.1272.

    Article  CAS  PubMed  Google Scholar 

  39. Vu, Anh Tuan, Tadashi Baba, Xue Chen, Tuan Anh Le, Hirokazu Kinoshita, Yang Xie, Seiji Kamijo, et al. 2010. Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2–Toll-like receptor 6 pathway. Journal of Allergy and Clinical Immunology 126: 985–993.e3. https://doi.org/10.1016/j.jaci.2010.09.002.

    Article  CAS  PubMed  Google Scholar 

  40. Martin, S.F., P.R. Esser, F.C. Weber, T. Jakob, M.A. Freudenberg, M. Schmidt, and M. Goebeler. 2011. Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy 66: 1152–1163. https://doi.org/10.1111/j.1398-9995.2011.02652.x.

    Article  CAS  PubMed  Google Scholar 

  41. Ahmad, Sheikh Fayaz, Mushtaq Ahmad Ansari, Khairy M.A.A. Zoheir, Saleh A. Bakheet, Hesham M. Korashy, Ahmed Nadeem, Abdelkader E. Ashour, and Sabry M. Attia. 2015. Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. Immunobiology 220. Elsevier GmbH.: 889–898. https://doi.org/10.1016/j.imbio.2015.01.008.

    Article  CAS  PubMed  Google Scholar 

  42. Takeshita, Keisuke, Katsuya Sakai, Kevin B. Bacon, and Florian Gantner. 2003. Critical role of histamine H4 receptor in leukotriene B4 production and mast cell-dependent neutrophil recruitment induced by zymosan in vivo. Journal of Pharmacology and Experimental Therapeutics 307: 1072–1078. https://doi.org/10.1124/jpet.103.057489.

    Article  CAS  PubMed  Google Scholar 

  43. Liu, Yong Jun. 2007. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation. Journal of Allergy and Clinical Immunology 120: 238–244. https://doi.org/10.1016/j.jaci.2007.06.004.

    Article  CAS  PubMed  Google Scholar 

  44. Yagami, Akiko, Naoki Kajiwara, Keisuke Oboki, Tatsukuni Ohno, Hideaki Morita, Susan W. Sunnarborg, Ko Okumura, Hideoki Ogawa, Hirohisa Saito, and Susumu Nakae. 2010. Amphiregulin is not essential for induction of contact hypersensitivity. Allergology international: official journal of the Japanese Society of Allergology 59: 277–284. https://doi.org/10.2332/allergolint.09-OA-0149.

    Article  CAS  Google Scholar 

  45. Biedermann, T., M. Kneilling, R. Mailhammer, K. Maier, C.A. Sander, G. Kollias, S.L. Kunkel, L. Hültner, and M. Röcken. 2000. Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. The Journal of Experimental Medicine 192: 1441–1452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ajuebor, M.N., A.M. Das, L. Virág, R.J. Flower, C. Szabó, and M. Perretti. 1999. Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. Journal of Immunology (Baltimore, Md. : 1950) 162: 1685–1691.

    CAS  Google Scholar 

  47. Foster, P.S., S.P. Hogan, A.J. Ramsay, K.I. Matthaei, and I.G. Young. 1996. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. The Journal of Experimental Medicine 183: 195–201. https://doi.org/10.1084/jem.183.1.195.

    Article  CAS  PubMed  Google Scholar 

  48. Jin, Haoli, Rui He, Michiko Oyoshi, and Raif S. Geha. 2009. Animal models of atopic dermatitis. The Journal of Investigative Dermatology 129: 31–40. https://doi.org/10.1038/jid.2008.106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sözen, S., M. Kısakürek, F. Yildiz, M. Gönültaş, and A.S. Dinçel. 2011. The effects of glutamine on hepatic ischemia reperfusion injury in rats. The Hip 15: 161–166.

    Google Scholar 

  50. Coruzzi, Gabriella, Cristina Pozzoli, Maristella Adami, Daniela Grandi, Nicoletta Guido, Rogier Smits, Iwan de Esch, and Rob Leurs. 2012. Strain-dependent effects of the histamine H4 receptor antagonist JNJ7777120 in a murine model of acute skin inflammation. Experimental Dermatology 21: 32–37. https://doi.org/10.1111/j.1600-0625.2011.01396.x.

    Article  CAS  PubMed  Google Scholar 

  51. Somma, T., L. Cinci, G. Formicola, A. Pini, R. Thurmond, M. Ennis, D. Bani, and E. Masini. 2013. A selective antagonist of histamine H4 receptors prevents antigen-induced airway inflammation and bronchoconstriction in guinea pigs: involvement of lipocortin-1. British Journal of Pharmacology 170: 200–213. https://doi.org/10.1111/bph.12264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Strakhova, M.I., C.A. Cuff, A.M. Manelli, T.L. Carr, D.G. Witte, J.L. Baranowski, T.A. Vortherms, et al. 2009. In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties. British Journal of Pharmacology 157. Wiley-Blackwell: 44–54. https://doi.org/10.1111/j.1476-5381.2009.00236.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Buckland, Karen F., Timothy J. Williams, and Dolores M. Conroy. 2003. Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. British Journal of Pharmacology 140: 1117–1127. https://doi.org/10.1038/sj.bjp.0705530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Barnard, Ruth, Adrian Barnard, Gary Salmon, Wai Liu, and Sasha Sreckovic. 2008. Histamine-induced actin polymerization in human eosinophils: an imaging approach for histamine H4 receptor. Cytometry Part A 73: 299–304. https://doi.org/10.1002/cyto.a.20514.

    Article  Google Scholar 

  55. Hines, Ian N., Jason M. Hoffman, Heleen Scheerens, Brian J. Day, Hirohisa Harada, Kevin P. Pavlick, Sulaiman Bharwani, et al. 2003. Regulation of postischemic liver injury following different durations of ischemia. American Journal of Physiology. Gastrointestinal and Liver Physiology 284: G536–G545. https://doi.org/10.1152/ajpgi.00400.2002.

    Article  CAS  PubMed  Google Scholar 

  56. Kapp, A., G. Zeck-Kapp, W. Czech, and E. Schöpf. 1994. The chemokine RANTES is more than a chemoattractant: characterization of its effect on human eosinophil oxidative metabolism and morphology in comparison with IL-5 and GM-CSF. The Journal of Investigative Dermatology 102: 906–914. https://doi.org/10.1111/1523-1747.ep12383399.

    Article  CAS  PubMed  Google Scholar 

  57. Dhar, Arindam, Mathew R. Young, and Nancy H. Colburn. 2002. The role of AP-1, NF-кB and ROS/NOS in skin carcinogenesis: the JB6 model is predictive. Molecular and Cellular Biochemistry 234–235: 185–193. https://doi.org/10.1023/A:1015948505117.

    Article  PubMed  Google Scholar 

  58. Folkerts, Gert, Joris Kloek, Richard B.R. Muijsers, and Frans P. Nijkamp. 2001. Reactive nitrogen and oxygen species in airway inflammation. European Journal of Pharmacology 429: 251–262. https://doi.org/10.1016/S0014-2999(01)01324-3.

    Article  CAS  PubMed  Google Scholar 

  59. Wakabayashi, Nobunao, Stephen L. Slocum, John J. Skoko, Soona Shin, and Thomas W. Kensler. 2010. When NRF2 talks, who’s listening? Antioxidants & Redox Signaling 13: 1649–1663. https://doi.org/10.1089/ars.2010.3216.

    Article  CAS  Google Scholar 

  60. Stocker, R., Y. Yamamoto, A.F. McDonagh, A.N. Glazer, and B.N. Ames. 1987. Bilirubin is an antioxidant of possible physiological importance. Science (New York, N.Y.) 235: 1043–1046. https://doi.org/10.1126/science.3029864.

    Article  CAS  Google Scholar 

  61. Nguyen, Truyen, H.C. Huang, and Cecil B. Pickett. 2000. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. Journal of Biological Chemistry 275: 15466–15473. https://doi.org/10.1074/jbc.M000361200.

    Article  CAS  PubMed  Google Scholar 

  62. Kensler, T.W., N. Wakabayashi, and S. Biswal. 2007. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annual Review of Pharmacology and Toxicology 47: 89–116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046.

    Article  CAS  PubMed  Google Scholar 

  63. Franklin, Christopher C., Donald S. Backos, Isaac Mohar, Collin C. White, Henry J. Forman, and Terrance J. Kavanagh. 2009. Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Molecular Aspects of Medicine 30: 86–98. https://doi.org/10.1016/j.mam.2008.08.009.

    Article  CAS  PubMed  Google Scholar 

  64. El Ali, Zeina, Cédric Gerbeix, Patrice Hemon, Philipp R. Esser, Stefan F. Martin, Marc Pallardy, and Saadia Kerdine-Römer. 2013. Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2. Toxicological Sciences 134: 39–48. https://doi.org/10.1093/toxsci/kft084.

    Article  PubMed  Google Scholar 

  65. Shen, Shiping, Jinquan Li, Huihui You, Wu Zhuo, Wu Yang, Yun Zhao, Yuqing Zhu, et al. 2017. Oral exposure to diisodecyl phthalate aggravates allergic dermatitis by oxidative stress and enhancement of thymic stromal lymphopoietin. Food and Chemical Toxicology 99: 60–69. https://doi.org/10.1016/j.fct.2016.11.016.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt

    Ahmed F. Mohamed, Mohammed F. El-Yamany & Mohamed T. Abdel-Aziz

  2. Department of Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Fatma A. El-Batrawy

Authors
  1. Ahmed F. Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammed F. El-Yamany
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatma A. El-Batrawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohamed T. Abdel-Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed F. Mohamed.

Ethics declarations

All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996) and were approved by the Ethics Committee for Animal Experimentation at Faculty of Pharmacy, Cairo University (PT 808).

Conflict of Interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohamed, A.F., El-Yamany, M.F., El-Batrawy, F.A. et al. JNJ7777120 Ameliorates Inflammatory and Oxidative Manifestations in a Murine Model of Contact Hypersensitivity via Modulation of TLR and Nrf2 Signaling. Inflammation 41, 378–389 (2018). https://doi.org/10.1007/s10753-017-0693-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-017-0693-3

KEY WORDS

Search

Navigation