Reciprocal Regulation of Thymus and Activation-Regulated Chemokine/Macrophage-Derived Chemokine Production by Interleukin (IL)-4/IL-13 and Interferon-γ in HaCaT Keratinocytes Is Mediated by Alternations in E-cadherin Distribution

Shoko Fujii-Maeda, Keiich Kajiwara, Kouichi Ikizawa, Miki Shinazawa, Bin Yu, Tetsuya Koga, Masutaka Furue, Yukiyoshi Yanagihara

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Keratinocytes produce many cytochemokines that are involved in the pathogenesis of skin disorders. In particular, the CC chemokines thymus and activation-regulated chemokine (TARC)/macrophage-derived chemokine (MDC) play an important role in the infiltration of Th2 cells. This study was undertaken to examine the regulatory effects of interleukin (IL)-4, IL-13, and Interferon (IFN)-γ on TARC/MDC production in the human keratinocyte cell line HaCaT. HaCaT cells spontaneously secrete TARC and MDC. The production of TARC/MDC was downregulated by IL-4/IL-13, whereas it was upregulated by IFN-γ. To explore these regulatory mechanisms, we investigated the capacity of cytokines to regulate expression of several adhesion molecules that may affect TARC/MDC production. Of the adhesion molecules examined, the constitutive surface expression of E-cadherin was downregulated by IL-4/IL-13, but was upregulated by IFN-γ. Moreover, disruption of the homophilic adherence of E-cadherin by anti-E-cadherin antibody or calcium chelation abolished the production of TARC/MDC. We further examined the distribution of the adherens junction complex composed of E-cadherin, α-catenin, β-catenin, and γ-catenin. IL-4/IL-13 decreased the levels of membrane staining for adherens junction proteins, whereas IFN-γ increased membrane staining. Taken together, these results suggest that IL-4/IL-13 and IFN-γ induce alternations in the distribution of adherens junctions in a different fashion and thereby contribute to the reciprocal regulation of TARC/MDC production.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalJournal of Investigative Dermatology
Volume122
Issue number1
DOIs
Publication statusPublished - Jan 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Reciprocal Regulation of Thymus and Activation-Regulated Chemokine/Macrophage-Derived Chemokine Production by Interleukin (IL)-4/IL-13 and Interferon-γ in HaCaT Keratinocytes Is Mediated by Alternations in E-cadherin Distribution'. Together they form a unique fingerprint.

Cite this