A mechanism for the up-regulation of the IL-8 gene expression in keratinocytes by all-trans retinoic acid

Yae Lee Chung, Tae Won Kang, Sung Min Oh, Seung Yong Chung, Soo Chan Kim

Research output: Contribution to journalArticle

Abstract

Background: Retinoic acid (RA) has been reported to induce the up-regulation of inflammatory cytokines such as IL-1, TNF-α and IL-8 in dermal fibroblasts and keratinocytes. There is no evidence to support a direct interaction between the RA-mediated transcriptional machinery and IL-8 gene transcription. Objective: The aim of this study is to clarify the mechanism of the up-regulation of IL-8 in keratinocytes by RA. Methods: The IL-1, IL-8, TNF-α and MCP-1 mRNA expressions in HaCaT cells stimulated by RA were measured by quantitative RT-PCR. The effects of a NF-κ B inhibitor and IL-1 receptor antagonist (ra) on the IL-8 mRNA expression were measured by quantitative RT-PCR. Electrophoretic motility shift assay (EMSA) was conducted on the RA-stimulated HaCaT cells that were or were not treated with NF-κ B inhibitor to measure the NF-κ B binding activity in each group. The phospho-I κ B activity in the HaCaT cells after stimulation with RA was also measured by Western blotting. Results: An up-regulation of the IL-8 gene expression by RA was demonstrated in the HaCaT cells. The inhibition assay revealed the involvement of the NF-κ B binding site of the IL-8 gene in the RA-enhanced promoter activity. EMSA demonstrated that RA enhanced the formation of the DNA-NF-κ B complex. There was no evidence to support IL-1 as an intermediate stimulus between the RA-mediated transcriptional machinery and IL-8 gene transcription. Western blot analysis revealed increased phospho-I κ B activity in the HaCaT cells after stimulation with RA. Conclusion: Our result suggested that the IL-8 gene expression of HaCaT cells after RA stimulation is caused by the activation of IKK and the dissociation of I κ B from NF-κ B and the transcription of NF-κ B in the nucleus.

Original languageEnglish
Pages (from-to)674-682
Number of pages9
JournalKorean Journal of Dermatology
Volume47
Issue number6
Publication statusPublished - 2009 Jun 1

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All Science Journal Classification (ASJC) codes

  • Dermatology

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