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Overexpression of fractalkine and its histopathological characteristics in primary pterygium

  • Meydan TuranEmail author
  • Gulay Turan
Inflammatory Disorders
  • 28 Downloads

Abstract

Purpose

This study aimed to evaluate the differences in the expressions of fractalkine in normal bulbar conjunctiva and primary pterygium tissues.

Methods

The study included 48 patients who had been operated on for primary pterygium. Histopathologically, the presence of epithelial atypia, epithelial hyperplasia, goblet cell hyperplasia, epithelial lymphocytic exocytosis, stromal inflammation, mast cell count, and stromal vascularity were evaluated in the primary pterygium tissues. An immunohistochemical fractalkine stain was applied to the primary pterygium tissue samples and normal bulbar conjunctival tissue samples.

Results

Primary pterygium and normal bulbar conjunctival tissue samples were histopathologically analyzed. Epithelial atypia, epithelial hyperplasia, epithelial lymphocytic exocytosis, stromal inflammation, stromal vascularity, and mast cell count were found to be significantly higher in the primary pterygium (p = 0.001, p = 0.002, p = 0.024, p = 0.007, p = 0.024, and p = 0.013, respectively). When evaluated in terms of fractalkine expression, the epithelial, vascular endothelial, and inflammatory cells were significantly higher in the primary pterygium (p ≤ 0.001, p = 0.002, p = 0.001, respectively). Moreover, compared to the normal bulbar conjunctiva, Ki-67 expression was significantly higher in the primary pterygium tissue samples.

Conclusion

Fractalkine might play a key role in the etiopathogenesis of pterygium. Fractalkine may be important in developing new treatment approaches.

Keywords

Pterygium Immunhystochemistry Fractalkine Ki-67 Conjunctiva Histopathology 

Notes

Acknowledgments

The study was supported by Scientific Investigations Foundation of Balikesir University (Project no: BAP. 2018/159).

Funding information

This study was funded by Scientific Investigations Foundation of Balikesir University (grant number 2018/159).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

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 (ethical committee of Balikesir University Medical Faculty (Date: 05.09.2018/reference no: 2018/144)) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

References

  1. 1.
    Di Girolamo N, Chui J, Coroneo MT et al (2004) Pathogenesis of pterygia: role of cytokines, growth factors and matrix metalloproteinases. Prog Retin Eye Res 23:195–228.  https://doi.org/10.1016/j.preteyeres.2004.02.002 CrossRefPubMedGoogle Scholar
  2. 2.
    Sekundo W, Droutsas K, Cursiefen C (2010) Operative techniques for surgical treatment of primary and recurrent pterygia. Ophthalmologe 107:525–528.  https://doi.org/10.1007/s00347-009-2099-6 CrossRefPubMedGoogle Scholar
  3. 3.
    Dzunic B, Jovanovic P, Zlatanovic G et al (2010) Comparative analysis of histopathological and clinical characteristics of pterygium. Vojnosanit Pregl 67:159–157.  https://doi.org/10.4103/2008-322X.183917 CrossRefPubMedGoogle Scholar
  4. 4.
    Golu T, Mogoanta L, Streba CT et al (2011) Pterygium: histological and immunohistochemical aspects. Romanian J Morphol Embryol 52:153–158Google Scholar
  5. 5.
    Kase S, Osaki M, Jin XH et al (2007) Increased expression of erythropoietin receptor in human pterygial tissues. Int J Mol Med 20:699–702.  https://doi.org/10.3892/ijmm.20.5.699 CrossRefPubMedGoogle Scholar
  6. 6.
    Kase S, Takahashi S, Sato I et al (2007) Expression of p27(KIP1) and cyclin D1, and cell proliferation in human pterygium. Br J Ophthalmol 91:958–961.  https://doi.org/10.1136/bjo.2006.110387 CrossRefPubMedGoogle Scholar
  7. 7.
    Tan DT, Liu YP, Sun L (2000) Flow cytometry measurements of DNA content in primary and recurrent pterygia. Invest Ophthalmol Vis Sci 41:1684–1686PubMedGoogle Scholar
  8. 8.
    D’Haese JG, Demir IE, Friess H et al (2010) Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential. Expert Opin Ther Targets 14:207–219.  https://doi.org/10.1517/14728220903540265 CrossRefPubMedGoogle Scholar
  9. 9.
    Usta A, Turan G, Sancakli Usta C et al (2018) Placental fractalkine immunoreactivity in preeclampsia and its correlation with histopathological changes in the placenta and adverse pregnancy outcomes. J Matern Fetal Neonatal Med 10:1–10.  https://doi.org/10.1080/14767058.2018.1505854 CrossRefGoogle Scholar
  10. 10.
    Ruth JH, Volin MV, Haines GK et al (2001) Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 44:1568–1581.  https://doi.org/10.1002/1529-0131(200107)44:7<1568::AID-ART280>3.0.CO;2-1 CrossRefPubMedGoogle Scholar
  11. 11.
    Ruze A, Zhao Y, Li H et al (2018) Low shear stress upregulates the expression of fractalkine through the activation of mitogen-activated protein kinases in endothelial cells. Blood Coagul Fibrinolysis 29:361–368.  https://doi.org/10.1097/MBC.0000000000000701 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sindhu S, Akhter N, Arefanian H et al (2017) Increased circulatory levels of fractalkine (CX3CL1) are associated with inflammatory chemokines and cytokines in individuals with type-2 diabetes. J Diabetes Metab Disord 16:15.  https://doi.org/10.1186/s40200-017-0297-3 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Siwetz M, Dieber-Rotheneder M, Cervar-Zivkovic M et al (2015) Placental fractalkine is up-regulated in severe early-onset preeclampsia. Am J Pathol 185:1334–1343.  https://doi.org/10.1016/j.ajpath.2015.01.019 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhou B, Xu H, Ni K et al (2016) Expression of chemokine XCL2 and CX3CL1 in lung cancer. Med Sci Monit 22:1560–1565.  https://doi.org/10.12659/MSM.895985 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zou Y, Li Y, Lu L et al (2013) Correlation of fractalkine concentrations in serum and synovial fluid with the radiographic severity of knee osteoarthritis. Ann Clin Biochem 50:571–575.  https://doi.org/10.1177/0004563213480494 CrossRefPubMedGoogle Scholar
  16. 16.
    Wojdasiewicz P, Poniatowski LA, Kotela A et al (2014) The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1: occurrence and potential role in osteoarthritis. Arch Immunol Ther Exp 62:395–403.  https://doi.org/10.1007/s00005-014-0275-0 CrossRefGoogle Scholar
  17. 17.
    Hannan NJ, Salamonsen LA (2008) CX3CL1 and CCL14 regulate extracellular matrix and adhesion molecules in the trophoblast: potential roles in human embryo implantation. Biol Reprod 79:58–65.  https://doi.org/10.1095/biolreprod.107.066480 CrossRefPubMedGoogle Scholar
  18. 18.
    Safi H, Kheirkhah A, Mahbod M et al (2016) Correlations Between Histopathologic Changes and Clinical Features in Pterygia. J Ophthalmic Vis Res 11:153–158.  https://doi.org/10.4103/2008-322X.183917 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Robinson LA, Nataraj C, Thomas DW et al (2000) A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. J Immunol 165:6067–6072.  https://doi.org/10.4049/jimmunol.165.11.6067 CrossRefPubMedGoogle Scholar
  20. 20.
    Raychaudhuri SP, Jiang WY, Farber EM (2001) Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine. Br J Dermatol 144:1105–1113.  https://doi.org/10.1046/j.1365-2133.2001.04219.x CrossRefPubMedGoogle Scholar
  21. 21.
    Rimaniol AC, Till SJ, Garcia G et al (2003) The CX3C chemokine fractalkine in allergic asthma and rhinitis. J Allergy Clin Immunol 112:1139–1146.  https://doi.org/10.1016/j.jaci.2003.09.041 CrossRefPubMedGoogle Scholar
  22. 22.
    Efsen E, Grappone C, DeFranco RM et al (2002) Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans. J Hepatol 37:39–47.  https://doi.org/10.1016/S0168-8278(02)00065-X CrossRefPubMedGoogle Scholar
  23. 23.
    Kobayashi T, Okamoto S, Iwakami Y et al (2007) Exclusive increase of CX3CR1+CD28-CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes. Inflamm Bowel Dis 13:837–846.  https://doi.org/10.1002/ibd.20113 CrossRefPubMedGoogle Scholar
  24. 24.
    Silverman MD, Zamora DO, Pan Y et al (2007) Constitutive and inflammatory mediator-regulated Fractalkine expression in human ocular tissues and cultured cells. Invest Ophthalmol Vis Sci 44:1608–1615.  https://doi.org/10.1167/iovs.02-0233 CrossRefGoogle Scholar
  25. 25.
    Rosenbaum JT, Becker MD, Smith JR (2000) Toward new therapies for ocular inflammation [in Spanish]. Arch Soc Esp Oftalmol 75:511–514PubMedGoogle Scholar
  26. 26.
    Magone MT, Whitcup SM (1999) Mechanisms of intraocular inflammation. Chem Immunol 73:90–119.  https://doi.org/10.1159/000058742 CrossRefPubMedGoogle Scholar
  27. 27.
    Egwuagu CE, Sztein J, Mahdi RM et al (1999) IFN-gamma increases the severity and accelerates the onset of experimental autoimmune uveitis in transgenic rats. J Immunol 162:510–517PubMedGoogle Scholar
  28. 28.
    Singh VK, Rai G (2001) Cytokines in posterior uveitis: an update. Immunol Res 23:59–74.  https://doi.org/10.1385/IR:23:1:59 CrossRefPubMedGoogle Scholar
  29. 29.
    Lacomba MS, Martin CM, Chamond RR et al (2000) Aqueous and serum interferon gamma, interleukin (IL) 2, IL-4, and IL-10 in patients with uveitis. Arch Ophthalmol 118:768–772.  https://doi.org/10.1001/archopht.118.6.768 CrossRefPubMedGoogle Scholar
  30. 30.
    Fraticelli P, Sironi M, Bianchi G et al (2001) Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J Clin Invest 107:1173–1181.  https://doi.org/10.1172/JCI11517 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Enriquez-de-Salamanca A, Castellanos E, Stern ME et al (2010) Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease. Mol Vis 16:862–873 <http://www.molvis.org/molvis/v16/a96>PubMedPubMedCentralGoogle Scholar
  32. 32.
    Denoyer A, Godefroy D, Celerier I et al (2012) CX3CL1 expression in the conjunctiva is involved in immune cell trafficking during toxic ocular surface inflammation. Mucosal Immunol 5:702–711.  https://doi.org/10.1038/mi.2012.43 CrossRefPubMedGoogle Scholar
  33. 33.
    Chui J, Coroneo MT, Tat LT et al (2011) Ophthalmic pterygium: a stem cell disorder with premalignant features. Am J Pathol 178:817–827.  https://doi.org/10.1016/j.ajpath.2010.10.037 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Butrus SI, Ashraf MF, Laby DM et al (1995) Increased numbers of mast cells in pterygia. Am J Ophthalmol 119:236–237.  https://doi.org/10.1016/S0002-9394(14)73882-6 CrossRefPubMedGoogle Scholar
  35. 35.
    Zhou WP, Zhu YF, Zhang B et al (2016) The role of ultraviolet radiation in the pathogenesis of pterygia (review). Mol Med Rep 14:3–15.  https://doi.org/10.3892/mmr.2016.5223 CrossRefPubMedGoogle Scholar
  36. 36.
    Pahl HL (1999) Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18:6853–6866.  https://doi.org/10.1038/sj.onc.1203239 CrossRefGoogle Scholar
  37. 37.
    Kennedy M, Kim KH, Harten B at al. (1997) Ultraviolet irradiation induces the production of multiple cytokines by human corneal cells. Invest Ophthalmol Vis Sci 38:2483–2491PubMedGoogle Scholar
  38. 38.
    Dong Y, Kase S, Dong Z et al (2016) Regulation of vascular endothelial growth factor-C by tumor necrosis factor-α in the conjunctiva and pterygium. Int J Mol Med 38:545–550.  https://doi.org/10.3892/ijmm.2016.2647 CrossRefPubMedGoogle Scholar
  39. 39.
    Ljubojevic V, Gajanin R, Amidzic L et al (2016) The expression and significance of p53 protein and Ki-67 protein in pterygium. Vojnosanit Pregl 73:16–20.  https://doi.org/10.2298/VSP140428124L CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyBalikesir Ataturk City HospitalBalikesirTurkey
  2. 2.Faculty of Medicine, Department of PathologyBalikesir UniversityBalikesirTurkey

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