title: Keratinocyte-derived IL-24 plays a role in the positive feedback regulation of epidermal inflammation in response to environmental and endogenous toxic stressors.
abstract: Keratinocytes are the major cellular components of human epidermis and play a key role in the modulating cutaneous inflammation and toxic responses. In human chronic skin diseases, the common skin inflammatory phenotypes like skin barrier disruption and epidermal hyperplasia are manifested in epidermal keratinocytes by interactions with T helper (Th) cells. To find a common gene expression signature of human keratinocytes in chronic skin diseases, we performed a whole genome microarray analysis on normal human epidermal keratinocytes (NHKs) treated with IFNγ, IL-4, IL-17A or IL-22, major cytokines from Th1, Th2, Th17 or Th22 cells, respectively. The microarray results showed that the four genes, IL-24, PDZK1IP1, H19 and filaggrin, had common expression profiles in NHKs exposed to Th cell cytokines. In addition, the acute phase pro-inflammatory cytokines, IL-1β, IL-6 and TNFα, also change the gene transcriptional profile of IL-24, PDZK1IP1, H19, and filaggrin in NHKs as those of Th cytokines. Therefore, the signature gene set, consisting of IL-24, PDZK1IP1, H19, and filaggrin, provides essential insights for understanding the process of cutaneous inflammation and toxic responses. We demonstrate that environmental toxic stressors, such as chemical irritants and ultraviolet irradiation stimulate the production of IL-24 in NHKs. IL-24 stimulates the JAK1-STAT3 and MAPK pathways in NHKs, and promotes the secretion of pro-inflammatory mediators IL-8, PGE2, and MMP-1. These results suggest that keratinocyte-derived IL-24 participates in the positive feedback regulation of epidermal inflammation in response to both endogenous and environmental toxic stressors.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Jin
authors.affiliation: Department of Public Health Science, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Dalwoong
authors.initials: D
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul 156-756; Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Chun
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: minsoo@alum.mit.edu.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
mesh_terms: D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004817:Epidermis / Q000473:pathology*; D025461:Feedback, Physiological; D000091344:Filaggrin Proteins; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology*; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000502:physiology; D059467:Transcriptome; D000099180:Interleukin-24
chemical_list: D015232:Dinoprostone; D000091344:Filaggrin Proteins; D007371:Interferon-gamma; D016209:Interleukin-8; D007378:Interleukins; D020781:Matrix Metalloproteinase 1; D050796:STAT3 Transcription Factor; D000099180:Interleukin-24; C000717249:FLG protein, human; C494086:STAT3 protein, human
keywords: Cutaneous inflammation; Human keratinocytes; IL-24; Irritants; Signal transducer and activator of transcription; T helper cell cytokines