Differential IL-10 receptor gene expression in acute versus chronic atopic eczema. Modulation by immunosuppressive drugs and cytokines in normal cultured keratinocytes

Inflamm Res. 1999 Oct;48(10):539-43. doi: 10.1007/s000110050500.

Abstract

Objective and design: The effects of the anticytokine interleukin 10 (IL-10) are mediated by specific receptors. In this study we examined the role of the IL-10 receptor (IL-10R) in the pathophysiology of atopic eczema.

Materials and methods: For this purpose we analyzed the expression of IL-10R in the skin of patients with acute and chronic atopic eczema in comparison to the expression in healthy individuals using in situ binding experiments with fluorescently labeled IL-10 and semiquantitative reverse transcriptase-PCR specific for IL-10R1. In addition, we studied the influence of the Th2-associated cytokine interleukin-4 (IL-4), the Th1-associated gamma-interferon (IFN-gamma), the immunosuppressive drug FK506, the H1-antagonist loratadine and UVA irradiation on the expression of IL-10R1 in cultured normal human keratinocytes.

Results: We found that IL-10 receptor mRNA and protein are strongly downregulated in acute phase atopic lesions. Furthermore we could show that IL-4, IFN-gamma, FK506, loratadine and UVA enhance the mRNA levels of the IL-10R1 in vitro in normal cultured keratinocytes. We could also demonstrate restored IL-10R1 mRNA levels in lesional atopic skin of a patient after UVA1 therapy.

Conclusions: Our results demonstrate for the first time that IL-10 receptors may have a role in the pathogenesis of atopic eczema and its upregulation by FK506 and UVA could explain the therapeutic efficacy of these agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Cells, Cultured
  • Chronic Disease
  • Cytokines / genetics
  • Cytokines / pharmacology
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / physiopathology*
  • Dermatitis, Atopic / radiotherapy
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Keratinocytes / drug effects*
  • Keratinocytes / radiation effects
  • Middle Aged
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • RNA, Messenger / radiation effects
  • Receptors, Interleukin / analysis
  • Receptors, Interleukin / drug effects
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / radiation effects
  • Receptors, Interleukin-10
  • Tacrolimus / pharmacology
  • Ultraviolet Therapy

Substances

  • Cytokines
  • Immunosuppressive Agents
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Tacrolimus