title: UVB-irradiated human keratinocytes and interleukin-1alpha indirectly increase MAP kinase/AP-1 activation and MMP-1 production in UVA-irradiated dermal fibroblasts.
abstract: BACKGROUND
  Solar ultraviolet (UV) irradiation induces the production of matrix metalloproteinases (MMPs) by activating cellular signalling transduction pathways. MMPs are responsible for the degradation and/or inhibition of synthesis of collagenous extracellular matrix in connective tissues. We mimicked the action of environmental ultraviolet on skin and investigated the effects of UVB-irradiated human keratinocytes HaCaT and IL-1alpha on mitogen activated protein (MAP) kinase activation, c-Jun and c-Fos (AP-1 is composed of Jun and Fos proteins) mRNA expression and MMP-1 production in UVA-irradiated dermal fibroblasts.
  
  
  METHODS
  Following UVA irradiation, the culture medium of fibroblasts was replaced by culture medium from UVB-irradiated HaCaT, or replaced by the complete culture medium with interleukin (IL)-1alpha. MAP kinase activity expression in fibroblasts was detected by Western blot. c-Jun and c-Fos mRNA expressions were determined by reverse transcriptional polymerase chain reaction (RT-PCR); MMP-1 production in culture medium was detected by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Culture medium from UVB-irradiated keratinocytes increased MAP kinase activity and c-Jun mRNA expression in UVA-irradiated fibroblasts. IL-1alpha increased MAP kinase activity and c-Jun mRNA expression, IL-1alpha also increased c-Fos mRNA expression. Both culture media from UVB-irradiated human keratinocytes and externally applied IL-1alpha increased MMP-1 production in UVA-irradiated fibroblasts.
  
  
  CONCLUSIONS
  UVB-irradiated keratinocytes and IL-1alpha indirectly promote MMP-1 production in UVA-irradiated fibroblasts by increasing MAP kinase/AP-1 activity. IL-1 may play an important role in the paracrine activation and dermal collagen excessive degradation leading to skin photoaging.
authors.affiliation: Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiao-yong
authors.initials: XY
authors.lastname: Wang
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Bi
mesh_terms: D002460:Cell Line; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000528:radiation effects*; D015595:Skin Aging; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1