IL-32 promotes the occurrence of atopic dermatitis by activating the JAK1/microRNA-155 axis

J Transl Med. 2022 May 11;20(1):207. doi: 10.1186/s12967-022-03375-x.

Abstract

Background: This study aims to explore the mechanism of interleukin-32 (IL-32) affecting atopic dermatitis (AD) through the Janus-activated kinase-1 (JAK1)/microRNA-155 (miR-155) axis.

Methods: In this study, skin tissue samples and blood samples from normal subjects and patients with AD, human immortalized keratinocytes (HaCaT), and PA-induced mouse models of AD were selected for expression determination of IL-32, JAK1 and miR-155. The interaction among IL-32, JAK1 and miR-155 was identified with their roles in AD analyzed through loss- and gain-of-function assays.

Results: Elevated IL-32 was detected in AD tissues and blood samples and promoted the occurrence of AD. IL-32 upregulated JAK1 expression and phosphorylation of its downstream genes, thus activating the JAK signaling pathway. JAK1 promoted the expression of miR-155. IL-32/JAK1/miR-155 axis promoted inflammation in the AD skin reconstruction model. In vivo experiments further confirmed that IL-32 promoted AD development by activating the JAK1/miR-155 axis.

Conclusion: The present study underlined that IL-32 promoted the occurrence of AD by promoting JAK1 expression to upregulate miR-155 expression.

Keywords: Atopic dermatitis; Human immortalized keratinocytes; Inflammation; Interleukin-32; Janus-activated kinase-1; Phosphorylation; Skin reconstruction model; microRNA-155.

MeSH terms

  • Animals
  • Dermatitis, Atopic* / genetics
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism
  • Janus Kinase 1 / genetics
  • Janus Kinase 1 / metabolism
  • Keratinocytes / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Skin / metabolism

Substances

  • IL32 protein, human
  • Interleukins
  • MIRN155 microRNA, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • interleukin-32, mouse
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1