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Upregulation of NLRP3 inflammasome components in Mooren’s ulcer

  • Inflammatory Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Mooren’s ulcer (MU) is a peripheral corneal ulceration of presumed autoimmune etiology. NLRP3 inflammasome has been shown to be involved in a variety of autoimmune and auto-inflammatory diseases. However, the role of NLRP3 inflammasome in MU has not been investigated. Here, we evaluate the expression of NLRP3 inflammasome and its downstream inflammatory factors in human MU.

Methods

Conjunctival biopsy specimens were obtained from seven patients with MU and six healthy donors. The removed conjunctivas were histopathologically evaluated for NLRP3 inflammasome component expression using antibodies directed against NLRP3, Caspase-1 (CASP1), and Interleukin-1β (IL-1β). Quantitative real-time PCR was used to measure the mRNA expression of NLRP3 and IL-1β, and the protein expressions of NLRP3, pro-CASP1, CASP1, and IL-1β were detected by Western blotting.

Results

NLRP3 and IL-1β mRNA expression showed higher levels in the MU group than in healthy controls. Western-blot and immunofluorescence analysis also showed that basal expression of NLRP3 inflammasome components (NLRP3, CAPS1, and IL-1β) was elevated in patients with MU compared with healthy controls. Most importantly, we found that the cleavaged form of CASP1 and IL-1β was significantly increased in MU patients compared with healthy donors, which indicates that the upregulation of NLRP3 inflammasome was probably responsible for the enhanced IL-1β production in MU patients.

Conclusions

This study demonstrated that the expression of the NLRP3-CASP1-IL-1β signaling pathway was markedly increased in the conjunctival lesions of patients with MU, suggesting the involvement of NLRP3 inflammasome in the onset and development of the inflammation in MU.

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References

  1. Foster CS, Kenyon KR, Greiner J, Greineder DK, Friedland B, Allansmith MR (1979) The immunopathology of Mooren’s ulcer. Am J Ophthalmol 88:149–159

    Article  CAS  PubMed  Google Scholar 

  2. Ye J, Chen J, Kim JC, Yao K (2004) Bone marrow-derived cells are present in Mooren’s ulcer. Ophthalmic Res 36:151–155

    Article  PubMed  Google Scholar 

  3. Kafkala C, Choi J, Zafirakis P, Baltatzis S, Livir-Rallatos C, Rojas B, Foster CS (2006) Mooren ulcer: an immunopathologic study. Cornea 25:667–673

    Article  PubMed  Google Scholar 

  4. Shinomiya K, Ueta M, Sotozono C, Inatomi T, Yokoi N, Koizumi N, Kinoshita S (2013) Immunohistochemical analysis of inflammatory limbal conjunctiva adjacent to Mooren’s ulcer. Br J Ophthalmol 97:362–366

    Article  PubMed  Google Scholar 

  5. Lee HJ, Kim MK, Wee WR, Oh JY (2015) Interplay of immune cells in Mooren ulcer. Cornea 34:1164–1167

    Article  PubMed  Google Scholar 

  6. Brown SI, Mondino BJ, Rabin BS (1976) Autoimmune phenomenon in Mooren’s ulcer. Am J Ophthalmol 82:835–840

    Article  CAS  PubMed  Google Scholar 

  7. Gottsch JD, Liu SH, Minkovitz JB, Goodman DF, Srinivasan M, Stark WJ (1995) Autoimmunity to a cornea-associated stromal antigen in patients with Mooren’s ulcer. Invest Ophthalmol Vis Sci 36:1541–1547

    CAS  PubMed  Google Scholar 

  8. Foster CS (1985) Systemic immunosuppressive therapy for progressive bilateral Mooren’s ulcer. Ophthalmology 92:1436–1439

    Article  CAS  PubMed  Google Scholar 

  9. Zhao J, Jin X (1992) Treatment of severe Mooren’s ulcer with cyclosporin A eyedrops. Chin Med J 105:406–409

    CAS  PubMed  Google Scholar 

  10. Kinoshita S, Ohashi Y, Ohji M, Manabe R (1991) Long-term results of keratoenpithelioplasty in Mooren’s ulcer. Ophthalmology 98:438–445

    Article  CAS  PubMed  Google Scholar 

  11. Chen G, Shaw MH, Kim Y-G, Nuñez G (2009) NOD-like receptors: role in innate immunity and inflammatory disease. Annu Rev Pathol Mech Dis 4:365–398

    Article  CAS  Google Scholar 

  12. Martinon F, Mayor A, Tschopp J (2009) The inflammasomes: guardians of the body. Annu Rev Immunol 27:229–265

    Article  CAS  PubMed  Google Scholar 

  13. Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell 10:417–426

    Article  CAS  PubMed  Google Scholar 

  14. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J (2004) NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle–Wells autoinflammatory disorder. Immunity 20:319–325

    Article  CAS  PubMed  Google Scholar 

  15. Im H, Ammit A (2014) The NLRP3 inflammasome: role in airway inflammation. Clin Exp Allergy 44:160–172

    Article  CAS  PubMed  Google Scholar 

  16. Andersen K, Eltrich N, Lichtnekert J, Anders H-J, Vielhauer V (2014) The NLRP3/ASC inflammasome promotes T-cell-dependent immune complex glomerulonephritis by canonical and noncanonical mechanisms. Kidney Int 86:965–978

    Article  CAS  PubMed  Google Scholar 

  17. Jankovic D, Ganesan J, Bscheider M, Stickel N, Weber FC, Guarda G, Follo M, Pfeifer D, Tardivel A, Ludigs K (2013) The Nlrp3 inflammasome regulates acute graft-versus-host disease. J Exp Med 210:1899–1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kahlenberg JM, Kaplan MJ (2014) The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis? Curr Opin Rheumatol 26:475–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Benetti E, Chiazza F, Patel NS, Collino M (2013) The NLRP3 Inflammasome as a novel player of the intercellular crosstalk in metabolic disorders. Mediat Inflamm. doi:10.1155/2013/678627

    Google Scholar 

  20. Rock KL, Kataoka H, Lai J-J (2013) Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol 9:13–23

    Article  CAS  PubMed  Google Scholar 

  21. Marneros AG (2013) NLRP3 inflammasome blockade inhibits VEGF-A-induced age-related macular degeneration. Cell Rep 4:945–958

    Article  CAS  PubMed  Google Scholar 

  22. Doyle SL, Campbell M, Ozaki E, Salomon RG, Mori A, Kenna PF, Farrar GJ, Kiang A-S, Humphries MM, Lavelle EC (2012) NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nat Med 18:791–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lamkanfi M, Dixit VM (2012) Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol 28:137–161

    Article  CAS  PubMed  Google Scholar 

  24. Zelefsky JR, Srinivasan M, Cunningham ET (2011) Mooren’s ulcer. Exp Rev Ophthalmol 6:461–467

    Article  Google Scholar 

  25. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, 5 Yanerdao Road, Qingdao, 266071, China

    Zhiyuan Li, Chao Wei, Shuang Wang, Ting Liu, Hualei Zhai & Weiyun Shi

Authors
  1. Zhiyuan Li
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  2. Chao Wei
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  3. Shuang Wang
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  4. Ting Liu
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  5. Hualei Zhai
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  6. Weiyun Shi
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Corresponding author

Correspondence to Chao Wei.

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Funding

The National Natural Science Foundation of China provided financial support in the form of funds from the National Natural Science Foundation of China (81500767, 81530027, 81370989, and 81500703). The Department of Science Technology of Shandong province provided financial support in the form of the Young and Middle-Aged scientists Research Awards Fund of Shandong Province (ZR2015PH008 and BS2014YY003). The Shandong Academy of Medical Sciences provided financial support in the form of funds from the Innovation Project of Shandong Academy of Medical Sciences. The sponsors had no role in the design or conduct of this research.

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Animal experiments

This article does not contain any studies with animals performed by any of the authors.

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Li, Z., Wei, C., Wang, S. et al. Upregulation of NLRP3 inflammasome components in Mooren’s ulcer. Graefes Arch Clin Exp Ophthalmol 255, 607–612 (2017). https://doi.org/10.1007/s00417-016-3516-6

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  • DOI: https://doi.org/10.1007/s00417-016-3516-6

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