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IL28RA inhibits human epidermal keratinocyte proliferation by inhibiting cell cycle progression

  • Xueli Yin
  • Shengquan Zhang
  • Bao Li
  • Yaohua Zhang
  • Xuejun Zhang
Original Article
  • 33 Downloads

Abstract

Interleukin (IL) 28 receptor α (IL28RA) is a well-known candidate for psoriasis susceptibility based on previous genome-wide association study (GWAS) analysis. However, the function of IL28RA in psoriasis has not been elucidated. In the present study, the expression of IL28RA was significantly decreased in lesional tissues from patients with plaque psoriasis when compared with the expression observed in adjacent non-lesional tissues. In vitro studies further demonstrated that in the presence of IL-29, HaCaT keratinocytes with IL28RA knockdown exhibited a faster rate of proliferation than control cells, and an enhanced ratio of cells in the S and G2/M phase. By contrast, IL28RA overexpression inhibited the proliferation of HaCaT keratinocytes and caused cell cycle arrest at the G0/G1 phases. Western blot analysis revealed that knockdown of IL28RA upregulated cyclinB1 expression and downregulated cyclinE expression; the opposite results were observed in the IL28RA-overexpressing HaCaT cells. Finally, a mechanistic study revealed that IL28RA functions through the activation of the Janus kinase-signal transducer and activator of transcription signaling pathway to exert its anti-proliferative effect. These results suggested that weak expression of IL28RA may contribute to the pathogenesis of psoriasis and that IL28RA may be an effective drug target for the treatment of psoriasis. However, further in vivo studies are required.

Keywords

Psoriasis Interleukin 28 receptor α Proliferation Interleukin-29 Signaling pathway 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81130031 and 81602397) and the Natural Science Foundation of Shanghai (Grant No. 15ZR1405700). Grant Recipient: Xuejun Zhang, Yaohua Zhang.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Institute of Dermatology and Department of Dermatology, The First Affiliated HospitalAnhui Medical UniversityHefeiChina
  2. 2.Key Laboratory of Dermatology, Anhui Medical UniversityMinistry of EducationHefeiChina
  3. 3.Department of Biochemistry and Molecular Biology, School of Basic Medical SciencesAnhui Medical UniversityHefeiChina
  4. 4.Institute of Dermatology, Huashan HospitalFudan UniversityShanghaiChina

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