Trends in Immunotherapy

Article

Activation of proteinase-activated receptor-2 (PAR-2) simultaneously induces interleukin 8 (IL-8) and suppresses monocyte chemoattractant protein-1 (MCP-1) in HaCaT cells

Downloads

https://doi.org/10.24294/ti.v6.i1.1472
Murakami, Y., Azuma, S., Baba, K., Taniguchi, M., & Furukawa, F. (2022). Activation of proteinase-activated receptor-2 (PAR-2) simultaneously induces interleukin 8 (IL-8) and suppresses monocyte chemoattractant protein-1 (MCP-1) in HaCaT cells. Trends in Immunotherapy, 6(1). https://doi.org/10.24294/ti.v6.i1.1472
Volume 6 Issue 1 (2022)

Copyright

The authors shall retain the copyright of their work but allow the Publisher to publish, copy, distribute, and convey the work.

License

Trends in Immunotherapy (TI)  publishes accepted manuscripts under Creative Commons Attribution 4.0 International (CC BY 4.0). Authors who submit their papers for publication by TI agree to have the CC BY 4.0 license applied to their work, and that anyone is allowed to reuse the article or part of it free of charge for any purpose, including commercial use. As long as the author and original source are properly cited, anyone may copy, redistribute, reuse, and transform the content.

Authors

  • Yoshinobu Murakami
    Department of Aesthetics and Health Sciences, Wakayama Medical University Department of Natural Products Research, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University
  • Seisho Azuma
  • Kimiye Baba
  • Masahiko Taniguchi
  • Fukumi Furukawa Takatsuki Red Cross Hospital

Allergic diseases are currently considered diseases of excessive type 2 inflammation created by orchestration between the innate and acquired immune systems. Since pattern recognition receptors (PRRs) are present in epidermal keratinocytes, it is noteworthy that aggravating factors of allergic diseases act directly on keratinocytes via PRRs. To investigate the relationship between the activation of PRRs and inflammation, we stimulated a keratinocyte cell line (HaCaT cells) with agonists against proteinase-activated receptor-2 (PAR-2), Toll-like receptor (TLR)2, and TLR4, alone or in combination, and we evaluated the changes in inflammatory cytokines and chemokines. Activation of TLR2 or TLR4 alone induced interleukin 6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) in an agonist concentration-dependent manner. Simultaneous activation of TLR2 and TLR4 induced IL-8 synergistically, MCP-1 in an additive trend, and IL-6 weakly but synergistically. PAR-2 activation of HaCaT cells induced IL-6 and IL-8 but suppressed MCP-1 in an agonist concentration-dependent manner. The enhancement of IL-8 and the suppression of MCP-1 by PAR-2 activation were both neutralized by the PAR-2 antagonist AZ3451, supporting the possibility that PAR-2 activation simultaneously induces the following opposing effects in inflammation: enhancement of IL-8 and suppression of MCP-1. The nuclear factor-κB (NF-κB) pathway inhibitor BAY 11-7082 neutralized the induction of IL-8 but not the suppression of MCP-1 by PAR-2 activation, indicating that PAR-2 activation induces activation of the NF-κB pathway, and that the suppression of MCP-1 by PAR-2 activation is not related to the NF-κB pathway.

Keywords:

Pattern Recognition Receptor (PRR) Proteinase-activated Receptor-2 (PAR-2) Inflammation Allergic Diseases In-duced Interleukin 8 (IL-8) Monocyte Chemoattractant Protein-1 (MCP-1)

References

  1. Honda T, Kabashima K. Reconciling innate and acquired immunity in atopic dermatitis. Journal of Allergy and Clinical Immunology 2020; 145(4): 1136–1137. doi: 10.1016/j.jaci.2020.02.008
  2. Thiriou D, Morianos I, Xanthou G, et al. Innate immunity as the orchestrator of allergic airway inflammation and resolution in asthma. International Immunopharmacology 2017; 48: 43–54. doi: 10.1016/j.intimp.2017.04.027
  3. Jacquet A. The role of the house dust mite-induced innate immunity in development of allergic response. International Archives of Allergy and Immunology 2011; 155(2): 95–105. doi: 10.1159/000320375
  4. Wang JY. The innate immune response in house dust mite-induced allergic inflammation. Allergy, Asthma & Immunology Research 2013; 5(2): 68–74. doi: 10.4168/aair.2013.5.2.68
  5. Matsuwaki Y, Wada K, White T, et al. Alternaria fungus induces the production of GM-CSF, interleukin-6 and interleukin-8 and calcium signaling in human airway epithelium through protease-activated receptor 2. International Archives of Allergy and Immunology 2012; 158(Suppl 1): 19–29. doi: 10.1159/000337756
  6. Hayes T, Rumore A, Howard B, et al. Innate immunity induced by the major allergen Alt a 1 from the fungus Alternaria is dependent upon toll-like receptors 2/4 in human lung epithelial cells. Frontiers in Immunology 2018; 9: 1507. doi: 10.3389/fimmu.2018.01507
  7. Bitschar K, Wolz C, Krismer B, et al. Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin. Journal of Dermatological Science 2017; 87(3): 215–220. doi: 10.1016/j.jdermsci.2017.06.003
  8. Köllisch G, Kalali BN, Voelcker V, et al. Various members of the Toll-like receptor family contribute to the innate immune response of human epidermal keratinocytes. Immunology 2005; 114(4): 531–541. doi: 10.1111/j.1365-2567.2005.02122.x
  9. Chieosilapatham P, Kiatsurayanon C, Umehara Y, et al. Keratinocytes: Innate immune cells in atopic dermatitis. Clinical & Experimental Immunology 2021; 204(3): 296–309. doi: 10.1111/cei.13575
  10. Boonpiyathad T, Sözener ZC, Satitsuksanoa P, et al. Immunologic mechanisms in asthma. Seminars in Immunology 2019; 46: 101333. doi: 10.1016/j.smim.2019.101333
  11. Azuma S, Murakami Y, Azuma E, et al. Anti-inflammatory effects of flavonoids in Citrus jabara fruit peels. Trends in Immunotherapy 2020; 4(1): 5–14. doi: 10.24294/ti.v2i2.844
  12. Inaba Y, Furukawa F, Azuma S, et al. Evaluation of the safety and usefulness of Citrus jabara fruit peel powder cream for patients with atopic dermatitis. Trends in Immunotherapy 2020; 4(1): 42–46. doi: 10.24294/ti.v4.i1.1230
  13. Azuma S, Murakami Y, Taniguchi M, et al. Daily intake of Citrus jabara fruit peel powder (Japanese Patent No. 5,323,127) improves allergy-like symptoms: A randomized double-blind parallel-group comparative study. Trends in Immunotherapy 2020; 5(2): 21–31. doi: 10.24294/ti.v5.i2.1390
  14. Gregory LG, Lloyd CM. Orchestrating house dust mite-associated allergy in the lung. Trends in Immunology 2011; 32(9): 402–411. doi: 10.1016/j.it.2011.06.006
  15. Sato M, Sano H, Iwaki D, et al. Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-κB activation and TNF-α secretion are down-regulated by lung collectin surfactant protein A. The Journal of Immunology 2003; 171(1): 417–425. doi: 10.4049/jimmunol.171.1.417
  16. Lee HM, Yuk JM, Shin DM, et al. Apurinic/apyrimidinic endonuclease 1 is a key modulator of keratinocyte inflammatory responses. The Journal of Immunology 2009; 183(10): 6839–6848. doi: 10.4049/jimmunol.0901856
  17. Olaru F, Jensen LE. Chemokine expression by human keratinocyte cell lines after activation of Toll-like receptors. Experimental Dermatology 2010; 19(8): e314–e316. doi: 10.1111/j.1600-0625.2009.01026.x
  18. Kim HY, Goo JH, Joo YA, et al. Impact on inflammation and recovery of skin barrier by nordihydroguaiaretic acid as a protease-activated receptor 2 antagonist. Biomolecules & Therapeutics 2012; 20(5): 463–469. doi: 10.4062/biomolther.2012.20.5.463
  19. Huang X, Ni B, Xi Y, et al. Protease-activated receptor 2 (PAR-2) antagonist AZ3451 as a novel therapeutic agent for osteoarthritis. Aging (Albany NY) 2019; 11(24): 12532–12545. doi: 10.18632/aging.102586
  20. Jia Q, Zang D, Yi J, et al. Cytokine expression in trichloroethylene-induced hypersensitivity dermatitis: An in vivo and in vitro study. Toxicology Letters 2012; 215(1): 31–39. doi: 10.1016/j.toxlet.2012.09.018
  21. Mukaida N, Harada A, Matsushima K. Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine & Growth Factor Reviews 1998; 9(1): 9–23. doi: 10.1016/s1359-6101(97)00022-1
  22. Hou L, Kapas S, Cruchley AT, et al. Immunolocalization of protease-activated receptor-2 in skin: Receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology 1998; 94(3): 356–362. doi: 10.1046/j.1365-2567.1998.00528.x
  23. Asaduzzaman M, Nadeem A, Arizmendi N, et al. Functional inhibition of PAR2 alleviates allergen-induced airway hyperresponsiveness and inflammation. Clinical & Experimental Allergy 2015; 45(12): 1844–1855. doi: 10.1111/cea.12628
  24. Moffatt JD, Jeffrey KL, Cocks TM. Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice. American Journal of Respiratory Cell and Molecular Biology 2002; 26(6): 680–684. doi: 10.1165/ajrcmb.26.6.4693
  25. Khoufache K, LeBouder F, Morello E, et al. Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-γ-dependent pathway. The Journal of Immunology 2009; 182(12): 7795–7802. doi: 10.4049/jimmunol.0803743
  26. Macfarlane SR, Sloss CM, Cameron P, et al. The role of intracellular Ca2+ in the regulation of proteinase-activated receptor-2 mediated nuclear factor κB signalling in keratinocytes. British Journal of Pharmacology 2005; 145(4): 535–544. doi: 10.1038/sj.bjp.0706204
  27. Liu CF, Drocourt D, Puzo G, et al. Innate immune response of alveolar macrophage to house dust mite allergen is mediated through TLR2/-4 co-activation. PLoS ONE 2013; 8(10): e75983. doi: 10.1371/journal.pone.0075983
  28. Vu AT, Chen X, Xie Y, et al. Extracellular double-stranded RNA induces TSLP via an endosomal acidification- and NF-κB-dependent pathway in human keratinocytes. Journal of Investigative Dermatology 2011; 131(11): 2205–2212. doi: 10.1038/jid.2011.185
  29. Le TA, Takai T, Vu AT, et al. Flagellin induces the expression of thymic stromal lymphopoietin in human keratinocytes via toll-like receptor 5. International Archives of Allergy and Immunology 2011; 155(1): 31–37. doi: 10.1159/000318679
  30. Vu AT, Baba T, Chen X, et al. 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 2010; 126(5): 985–993.e3. doi: 10.1016/j.jaci.2010.09.002
  31. Redhu D, Franke K, Kumari V, et al. Thymic stromal lymphopoietin production induced by skin irritation results from concomitant activation of protease-activated receptor 2 and interleukin 1 pathways. British Journal of Dermatology 2020; 182(1): 119–129. doi: 10.1111/bjd.17940
  32. Sumikawa Y, Asada H, Hoshino K, et al. Induction of beta-defensin 3 in keratinocytes stimulated by bacterial lipopeptides through toll-like receptor 2. Microbes and Infection 2006; 8(6): 1513–1521. doi: 10.1016/j.micinf.2006.01.008
  33. Maeda S, Maeda S, Ohno K, et al. Protease-activated receptor-2 induces proinflammatory cytokine and chemokine gene expression in canine keratinocytes. Veterinary Immunology and Immunopathology 2013; 153(1–2): 17–25. doi: 10.1016/j.vetimm.2013.01.018
  34. Cocks TM, Moffatt JD. Protease-activated receptor-2 (PAR2) in the airways. Pulmonary Pharmacology & Therapeutics 2001; 14(3): 183–191. doi: 10.1006/pupt.2001.0285.32