title: Opposing Effects of Zac1 and Curcumin on AP-1-Regulated Expressions of S100A7.
abstract: ZAC, an encoding gene mapped at chromosome 6q24-q25 within PSORS1, was previously found over-expressed in the lower compartment of the hyperplastic epidermis in psoriatic lesions. Cytokines produced in the inflammatory dermatoses may drive AP-1 transcription factor to induce responsive gene expressions. We demonstrated that mZac1 can enhance AP-1-responsive S100A7 expression of which the encoding gene was located in PSORS4 with HaCaT keratinocytes. However, the mZac1-enhanced AP-1 transcriptional activity was suppressed by curcumin, indicating the anti-inflammatory property of this botanical agent and is exhibited by blocking the AP-1-mediated cross-talk between PSORS1 and PSORS4. Two putative AP-1-binding sites were found and demonstrated to be functionally important in the regulation of S100A7 promoter activity. Moreover, we found curcumin reduced the DNA-binding activity of AP-1 to the recognition element located in the S100A7 promoter. The S100A7 expression was found to be upregulated in the lesioned epidermis of atopic dermatitis and psoriasis, which is where this keratinocyte-derived chemoattractant engaged in the pro-inflammatory feedback loop. Understanding the regulatory mechanism of S100A7 expression will be helpful to develop therapeutic strategies for chronic inflammatory dermatoses via blocking the reciprocal stimuli between the inflammatory cells and keratinocytes.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Biochemistry Department, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Biochemistry Department, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Cheng
authors.affiliation: Biochemistry Department, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Biochemistry Department, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Biochemistry Department, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chien-Ping
authors.initials: CP
authors.lastname: Chiang
authors.affiliation: School of Nursing, National Defense Medical Center, Taipei, Taiwan, ROC.|School of Nursing, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Biochemistry Department, National Defense Medical Center, Taipei, Taiwan, ROC.|Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wang
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D017382:Reactive Oxygen Species; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D003474:Curcumin