title: T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes.
abstract: BACKGROUND
  Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.
  
  
  METHODS
  HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.
  
  
  RESULTS
  IL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.
  
  
  CONCLUSIONS
  Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Di
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Rui-Qun
authors.initials: RQ
authors.lastname: Qi
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Huo
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Lyu
authors.forename: Yu-Xiao
authors.initials: YX
authors.lastname: Hong
authors.forename: Hong-Duo
authors.initials: HD
authors.lastname: Chen
authors.affiliation: Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Gao
mesh_terms: D053456:Caspase 14 / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism*; D000091344:Filaggrin Proteins; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000201:enzymology* / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000378:metabolism; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C508598:IL4 protein, human; D018793:Interleukin-13; D007381:Intermediate Filament Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015847:Interleukin-4; D007371:Interferon-gamma; D053456:Caspase 14
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