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Preliminary Study on Gene Expression of Chitinase-Like Cytokines in Human Airway Epithelial Cell Under Chitin and Chitosan Microparticles Treatment

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Abstract

Small-sized chitin and chitosan microparticles (MPs) reduce allergic inflammation. We examined the capacity of these glycans to stimulate A549 human airway epithelial cells to determine the feasibility of using of these glycans as allergic therapeutic modality. A549 cells were treated with MPs and then expressions levels of chitinase domain-containing 1 (CHID1) and chitinase 3-like 1 (CHI3L1) genes were determined by quantitative real-time PCR. IL-6 production was measured by ELISA. Chitin MPs resulted in upregulation of CHI3L1 expression by 35.7-fold while mRNA expression did not change with chitosan MPs. Compared to the untreated group, production of IL-6 was significantly decreased in the chitosan MPs-treated group, but chitin MPs treatment cause elevation of IL-6 level. This study demonstrates that chitin potently induces CHI3L1 expression, but chitosan is relatively inert. This effect and inhibition of pro-inflammatory cytokine (IL-6) suggest that chitosan MPs may possess more potential for therapeutic uses in human airway allergic inflammation.

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References

  1. Khoushab, F., and M. Yamabhai. 2010. Chitin research revisited. Marine Drugs 8: 1988–2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shibata, Y., I. Honda, J.P. Justice, M.R. Van Scott, R.M. Nakamura, and Q.N. Myrvik. 2001. Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice. Infection and Immunity 69: 6123–6130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Da Silva, C.A., D. Hartl, W. Liu, C.G. Lee, and J.A. Elias. 2008. TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation. Journal of Immunology 181: 4279–4286.

    Article  Google Scholar 

  4. Mori, T., M. Murakami, M. Okumura, T. Kadosawa, T. Uede, and T. Fujinaga. 2005. Mechanism of macrophage activation by chitin derivatives. Journal of Veterinary Medical Science 67: 51–56.

    Article  CAS  PubMed  Google Scholar 

  5. Shibata, Y., L.A. Foster, J.F. Bradfield, and Q.N. Myrvik. 2000. Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse. Journal of Immunology 164: 1314–1321.

    Article  CAS  Google Scholar 

  6. Da Silva, C.A., C. Chalouni, A. Williams, D. Hartl, C.G. Lee, and J.A. Elias. 2009. Chitin is a size-dependent regulator of macrophage TNF and IL-10 production. Journal of Immunology 182: 3573–3582.

    Article  Google Scholar 

  7. Nagatani, K., S. Wang, V. Llado, C.W. Lau, Z. Li, A. Mizoguchi, C.R. Nagler, Y. Shibata, H.C. Reinecker, J.R. Mora, and E. Mizoguchi. 2012. Chitin microparticles for the control of intestinal inflammation. Inflammatory Bowel Diseases 18: 1698–1710.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wagener, J., R.K. Malireddi, M.D. Lenardon, M. Koberle, S. Vautier, D.M. MacCallum, T. Biedermann, M. Schaller, M.G. Netea, T.D. Kanneganti, G.D. Brown, A.J. Brown, and N.A. Gow. 2014. Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation. PLoS Pathogen 10: e1004050.

    Article  Google Scholar 

  9. Ghotloo, S., M.H. Hoseini, M.H. Alimohammadian, V. Khaze, A. Memarnejadian, and A. Rostami. 2015. Immunomodulatory effects of chitin microparticles on Leishmania major-infected BALB/c mice. Parasitology International 64: 219–221.

    Article  CAS  PubMed  Google Scholar 

  10. Van Dyken, S.J., A. Mohapatra, J.C. Nussbaum, A.B. Molofsky, E.E. Thornton, S.F. Ziegler, A.N. McKenzie, M.F. Krummel, H.E. Liang, and R.M. Locksley. 2014. Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and gammadelta T cells. Immunity 40: 414–424.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bae, M.J., H.S. Shin, E.K. Kim, J. Kim, and D.H. Shon. 2013. Oral administration of chitin and chitosan prevents peanut-induced anaphylaxis in a murine food allergy model. International Journal of Biological Macromolecules 61: 164–168.

    Article  CAS  PubMed  Google Scholar 

  12. Chen, C.L., Y.M. Wang, C.F. Liu, and J.Y. Wang. 2008. The effect of water-soluble chitosan on macrophage activation and the attenuation of mite allergen-induced airway inflammation. Biomaterials 29: 2173–2182.

    Article  CAS  PubMed  Google Scholar 

  13. Lee, C.G., C.A. Da Silva, C.S. Dela Cruz, F. Ahangari, B. Ma, M.J. Kang, C.H. He, S. Takyar, and J.A. Elias. 2011. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annual Review of Physiology 73: 479–501.

    Article  CAS  PubMed  Google Scholar 

  14. Kzhyshkowska, J., A. Gratchev, and S. Goerdt. 2007. Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. Biomarker Insights 2: 128–146.

    PubMed  PubMed Central  Google Scholar 

  15. Allen, J.E., T.E. Sutherland, and D. Ruckerl. 2015. IL-17 and neutrophils: unexpected players in the type 2 immune response. Current Opinion in Immunology 34: 99–106.

    Article  CAS  PubMed  Google Scholar 

  16. Liu, C., Q. Li, X. Zhou, V.P. Kolosov, and J.M. Perelman. 2013. The chitinase-like protein YKL-40 increases mucin5AC production in human bronchial epithelial cells. Experimental Cell Research 319: 2866–2873.

    Article  CAS  PubMed  Google Scholar 

  17. Chupp, G.L., C.G. Lee, N. Jarjour, Y.M. Shim, C.T. Holm, S. He, J.D. Dziura, J. Reed, A.J. Coyle, P. Kiener, M. Cullen, M. Grandsaigne, M.C. Dombret, M. Aubier, M. Pretolani, and J.A. Elias. 2007. A chitinase-like protein in the lung and circulation of patients with severe asthma. New England Journal of Medicine 357: 2016–2027.

    Article  CAS  PubMed  Google Scholar 

  18. Kzhyshkowska, J., S. Mamidi, A. Gratchev, E. Kremmer, C. Schmuttermaier, L. Krusell, G. Haus, J. Utikal, K. Schledzewski, J. Scholtze, and S. Goerdt. 2006. Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway. Blood 107: 3221–3228.

    Article  CAS  PubMed  Google Scholar 

  19. Srivastava, Sh, and S.R. Dighe. 2012. Inhibitory Effect of E-RH-06 on HDM-induced Secretion of IL-6 and IL-8 in rhinitis. International Journal of Scientific and Research Publications 2: 1–6.

    Article  Google Scholar 

  20. Hoseini, M.H., M. Moradi, M.H. Alimohammadian, V.K. Shahgoli, H. Darabi, and A. Rostami. 2016. Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection. Parasitology International 65: 99–104.

    Article  CAS  PubMed  Google Scholar 

  21. Repetto, G., A. del Peso, and J.L. Zurita. 2008. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nature Protocols 3: 1125–1131.

    Article  CAS  PubMed  Google Scholar 

  22. Xiao, W.C., G. Meng, Y.M. Zhao, H.H. Yuan, T.T. Li, Y.Y. Peng, Y. Zhao, M. Luo, W.M. Zhao, Z.G. Li, and X.F. Zheng. 2014. Human Secreted Stabilin-1-Interacting Chitinase-like Protein Aggravates the Inflammation Associated With Rheumatoid Arthritis and Is a Potential Macrophage Inflammatory Regulator in Rodents. Arthritis & Rheumatology 66: 1141–1152.

    Article  CAS  Google Scholar 

  23. Lee, C.G., C.A. Da Silva, J.Y. Lee, D. Hartl, and J.A. Elias. 2008. Chitin regulation of immune responses: an old molecule with new roles. Current Opinion in Immunology 20: 684–689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ober, C., and G.L. Chupp. 2009. The chitinase and chitinase-like proteins: a review of genetic and functional studies in asthma and immune-mediated diseases. Current Opinion in Allergy and Clinical Immunology 9: 401–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Koch, B.E., J. Stougaard, and H.P. Spaink. 2015. Keeping track of the growing number of biological functions of chitin and its interaction partners in biomedical research. Glycobiology 25: 469–482.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gudmundsdottir, S., R. Lieder, O.E. Sigurjonsson, and P.H. Petersen. 2015. Chitosan leads to downregulation of YKL-40 and inflammasome activation in human macrophages. Journal of Biomedical Materials Research. Part A 103: 2778–2785.

    Article  CAS  PubMed  Google Scholar 

  27. Riabov, V., A. Gudima, N. Wang, A. Mickley, A. Orekhov, and J. Kzhyshkowska. 2014. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Frontiers in Physiology 5: 75.1–13.

    Article  Google Scholar 

  28. Lee, C.G., D. Hartl, G.R. Lee, B. Koller, H. Matsuura, C.A. Da Silva, M.H. Sohn, L. Cohn, R.J. Homer, A.A. Kozhich, A. Humbles, J. Kearley, A. Coyle, G. Chupp, J. Reed, R.A. Flavell, and J.A. Elias. 2009. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. Journal of Experimental Medicine 206: 1149–1166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ye, Y.L., Y.H. Chuang, and B.L. Chiang. 2011. Strategies of mucosal immunotherapy for allergic diseases. Cellular & Molecular Immunology 8: 453–461.

    Article  CAS  Google Scholar 

  30. Lundberg, E., L. Fagerberg, D. Klevebring, I. Matic, T. Geiger, J. Cox, C. Algenas, J. Lundeberg, M. Mann, and M. Uhlen. 2010. Defining the transcriptome and proteome in three functionally different human cell lines. Molecular Systems Biology 6: 450.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Murai, H., S. Okazaki, H. Hayashi, A. Kawakita, K. Hosoki, M. Yasutomi, S. Sur, and Y. Ohshima. 2015. Alternaria extract activates autophagy that induces IL-18 release from airway epithelial cells. Biochemical and Biophysical Research Communications 464: 969–974.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Mandana Sattari for kindly gifting IL-6 ELISA Kit and Hasan Darbandi Tamijani for excellent technical support. This study was part of the M.Sc. thesis of Masumeh Alimohammadi. The present article is financially supported by “Research Department of the School of medicine Shahid Beheshti University of Medical Sciences” (Grant No 6142).

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Masumeh Alimohammadi, Farshid Yeganeh & Mostafa Haji Molla Hoseini

  2. Department of Applied Cell Sciences, School of Advance Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farshid Yeganeh

  3. Phitochemistry Recearch Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mostafa Haji Molla Hoseini

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  1. Masumeh Alimohammadi
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Correspondence to Mostafa Haji Molla Hoseini.

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Alimohammadi, M., Yeganeh, F. & Haji Molla Hoseini, M. Preliminary Study on Gene Expression of Chitinase-Like Cytokines in Human Airway Epithelial Cell Under Chitin and Chitosan Microparticles Treatment. Inflammation 39, 1108–1115 (2016). https://doi.org/10.1007/s10753-016-0342-2

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