title: Epithelial-mesenchymal interaction during photodynamic therapy-induced photorejuvenation.
abstract: Recently, several clinical studies reported that the photodynamic therapy (PDT) has photorejuvenation effects on the aged skin. Previously, our group introduced evidence of direct effect of PDT on cultured fibroblast (FB). PDT directly stimulated FBs and induced collagen synthesis through activation of extracellular signal-regulated kinase. In this study, we investigated indirect effect of PDT on the human dermal FB during photorejuvenation focused on the epithelial-mesenchymal interaction between keratinocyte (KC) and FB. The "low-level PDT" condition was used for PDT therapy to the cultured KC. Various kinds of cytokines in the supernatants of KC were evaluated by enzyme-linked immunosorbent assay. FBs were stimulated with the KC-conditioned medium (KCM) taken after PDT. The mRNA level of matrix metalloproteinases (MMPs), transforming growth factor (TGF)-β and collagen type Iα in the FB, was determined by real-time polymerase chain reaction. Clinical phtorejuvenation effect was also evaluated from nine patients who had PDT to treat actinic keratoses. Among the FB-stimulating cytokines, a significant elevation of interleukin (IL)-1α, IL-6, and tumor necrosis factor-α level in KCM was noted after PDT compared with controls. After stimulating FB with KCM, the mRNA of MMP-1 was decreased and the mRNA of collagen type Iα was increased compare to control. Clinically, fine wrinkles significantly reduced after PDT. However, coarse wrinkles were not recovered significantly. In conclusion, increased collagen synthesis may be mediated not only by direct effect of PDT on FB but also by indirect effect of PDT on FB through cytokines from KC, such as IL-1α, IL-6, and tumor necrosis factor-α.
authors.affiliation: Department of Dermatology, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-749, Republic of Korea.
authors.forename: Sue Kyung
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-749, Republic of Korea.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea.
authors.forename: Gi-Bang
authors.initials: GB
authors.lastname: Koo
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-749, Republic of Korea. yousunkim@ajou.ac.kr.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea. yousunkim@ajou.ac.kr.
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon, 443-749, Republic of Korea. maychan@ajou.ac.kr.
authors.forename: You Chan
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015595:Skin Aging / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D017077:Culture Media, Conditioned; D016207:Cytokines; C508584:IL1A protein, human; C508600:IL6 protein, human; D053582:Interleukin-1alpha; D015850:Interleukin-6; D017319:Photosensitizing Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000622:Aminolevulinic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Epithelial–mesenchymal interaction; Fibroblasts; Keratinocytes; Photodynamic therapy; Photorejuvenation