Cellular and Molecular Life Sciences

, Volume 70, Issue 12, pp 2205–2220

Impaired nuclear translocation of glucocorticoid receptors: novel findings from psoriatic epidermal keratinocytes

  • Xiao-Yong Man
  • Wei Li
  • Jia-Qi Chen
  • Jiong Zhou
  • Lilla Landeck
  • Kai-Hong Zhang
  • Zhen Mu
  • Chun-Ming Li
  • Sui-Qing Cai
  • Min Zheng
Research Article

DOI: 10.1007/s00018-012-1255-3

Cite this article as:
Man, XY., Li, W., Chen, JQ. et al. Cell. Mol. Life Sci. (2013) 70: 2205. doi:10.1007/s00018-012-1255-3

Abstract

Psoriasis is a chronic proliferative skin disease and is usually treated with topical glucocorticoids, which act through the glucocorticoid receptor (GR), a component of the physiological systems essential for immune responses, differentiation, and homeostasis. To investigate the possible role of GR in the pathogenesis of psoriasis, normal and psoriatic lesional skin were recruited. Firstly, the immunolocalization of GR in the skin and cultured epidermal keratinocytes were determined by immunofluorescence. In normal skin and cultured human epidermal keratinocytes, intracellular GR is localized in the nuclei, while in psoriatic skin and cultured keratinocytes, GR is in the cytoplasm. Next, we investigated possible factors associated with the cytoplasmic distribution. We found that VEGF and IFN-γ led to impaired nuclear translocation of GR through p53 and microtubule-inhibitor, vincristine, and inhibited nuclear uptake of GR in normal keratinocytes. In addition to dexamethasone, interleukin (IL)-13 was also able to transfer GR into nuclei of psoriatic keratinocytes. Furthermore, discontinuation of dexamethasone induced cytoplasmic retention of GR in normal keratinocytes. In contrast, energy depletion of normal epidermal keratinocytes did not change the nuclear distribution of GR. To confirm our findings in vivo, an imiquimod-induced psoriasis-like skin mouse model was included. IL-13 ameliorated (but vincristine exacerbated) the skin lesions on the mouse. Taken together, our findings define that impaired nuclear translocation of GR is associated with VEGF, IFN-γ, p53, and microtubule. Therapeutic strategies designed to accumulate GR in the nucleus, such as IL-13, may be beneficial for the therapy of psoriasis.

Keywords

Glucocorticoid receptor Nuclear translocation Psoriasis Keratinocyte 

Abbreviations

GR

Glucocorticoid receptor

IL

Interleukin

GRE

Glucocorticoid response elements

Dex

Dexamethasone

GSK

Glycogen synthase kinase

VEGF

Vascular endothelial growth factor

IFN-γ

Interferon-γ

ACTH

Adrenocorticotropic hormone

HGF

Hepatocyte growth factor

TGF

Transforming growth factor

IMQ

Imiquimod

Supplementary material

18_2012_1255_MOESM1_ESM.docx (61 kb)
Supplementary material 1 (DOCX 61 kb)

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Xiao-Yong Man
    • 1
  • Wei Li
    • 1
  • Jia-Qi Chen
    • 1
  • Jiong Zhou
    • 1
  • Lilla Landeck
    • 2
  • Kai-Hong Zhang
    • 3
  • Zhen Mu
    • 3
  • Chun-Ming Li
    • 1
  • Sui-Qing Cai
    • 1
  • Min Zheng
    • 1
  1. 1.Department of Dermatology, Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Department of DermatologyUniversity of OsnabrueckOsnabrueckGermany
  3. 3.Department of Dermatology, Affiliated HospitalTaishan Medical CollegeTaishanChina

Personalised recommendations