TGF-β1 Expression by Proliferated Keratinocytes in the Skin of E-Irradiated Mice

In this study, we established a radiodermatitis animal model and investigated the change in immune cell proportions in the secondary lymphoid organs. The cells responsible for the increased transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) production in the lesions following irradiation were also investigated. The radiodermatitis model was constructed by locally exposing the posterior dorsal region of hairless-1 (HR-1) mice to 10 Gy electron (E)-ray/day for six consecutive days. The change in immune cell proportions was analyzed by FACS. Immunohistochemistry was carried out to detect the expression of cytokines and cell-specific markers in the skin. The proportions of antigen-presenting cells, T cells, and B cells in the lymph nodes and spleen were affected by E-irradiation. After irradiation, TGF-β1 and IL-17 were co-localized in the papillary region of the dermis with keratin-14 (K-14)-positive cells rather than with regulatory T cells (Treg). IL-10 was not co-stained with Treg, T helper 17 (Th17) cells, dendritic cells, or macrophages. Our data indicate that TGF-β1 is over-expressed mainly by proliferated keratinocytes in the lesions of a radiodermatitis animal model.

[1]  Hyunju Choi,et al.  Effects of Lavandula angustifolia Aroma on Electroencephalograms in Female Adults with Sleep Disorders , 2012 .

[2]  Sung-Ho Son,et al.  꽃송이버섯의 균사 생장을 위한 배지 조건 최적화 , 2012 .

[3]  M. Benderitter,et al.  Abdominal γ-radiation induces an accumulation of function-impaired regulatory T cells in the small intestine. , 2011, International journal of radiation oncology, biology, physics.

[4]  Francis J. Huber,et al.  Th17 cells express interleukin-10 receptor and are controlled by Foxp3⁻ and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. , 2011, Immunity.

[5]  T. Kanda,et al.  Distinct Roles of IL-23 and IL-17 in the Development of Psoriasis-Like Lesions in a Mouse Model , 2011, The Journal of Immunology.

[6]  C. Heldin,et al.  A decisive function of transforming growth factor-β/Smad signaling in tissue morphogenesis and differentiation of human HaCaT keratinocytes , 2011, Molecular biology of the cell.

[7]  Yanyong Yang,et al.  Gamma-ray Irradiation Impairs Dendritic Cell Migration to CCL19 by Down-regulation of CCR7 and Induction of Cell Apoptosis , 2011, International journal of biological sciences.

[8]  D. Nelson,et al.  Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro , 2011, International journal of radiation biology.

[9]  Tomoko Mori,et al.  Psoriasis and other Th17-mediated skin diseases. , 2010, Journal of UOEH.

[10]  J. O’Shea,et al.  Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. , 2010, Cytokine & growth factor reviews.

[11]  C. Tato,et al.  Innate IL-17-producing cells: the sentinels of the immune system , 2010, Nature Reviews Immunology.

[12]  A. Keegan,et al.  Regulation of the T helper cell type 2 (Th2)/T regulatory cell (Treg) balance by IL‐4 and STAT6 , 2010, Journal of leukocyte biology.

[13]  D. Douek,et al.  Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection , 2010, Nature Medicine.

[14]  V. Kuchroo,et al.  Interleukin-17 and type 17 helper T cells. , 2009, The New England journal of medicine.

[15]  Gisen Kim,et al.  Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis , 2009, Nature Immunology.

[16]  E. Shevach.  Mechanisms of foxp3+ T regulatory cell-mediated suppression. , 2009, Immunity.

[17]  X. Yang,et al.  Disruption of Smad4 in mouse epidermis leads to depletion of follicle stem cells. , 2008, Molecular biology of the cell.

[18]  V. Kuchroo,et al.  Induction and effector functions of TH17 cells , 2008, Nature.

[19]  Chen Dong,et al.  TH17 cells in development: an updated view of their molecular identity and genetic programming , 2008, Nature Reviews Immunology.

[20]  S. Sinha,et al.  A Functional Enhancer of Keratin14 Is a Direct Transcriptional Target of ΔNp63 , 2007 .

[21]  S. Sinha,et al.  A functional enhancer of keratin14 is a direct transcriptional target of deltaNp63. , 2007, The Journal of investigative dermatology.

[22]  E. Birgitte Lane,et al.  New consensus nomenclature for mammalian keratins , 2006, The Journal of cell biology.

[23]  Shimon Sakaguchi,et al.  Emerging possibilities in the development and function of regulatory T cells. , 2006, International immunology.

[24]  M. Cho,et al.  Altered immune cell proportions in the radiodermatitis induced hairless mice-1 (HR-1). , 2006, Journal of radiation research.

[25]  K. Mills,et al.  Regulatory T cells: friend or foe in immunity to infection? , 2004, Nature Reviews Immunology.

[26]  Elaine Fuchs,et al.  Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche , 2004, Cell.

[27]  A. Mamelak,et al.  The role of interleukin 10 in the pathogenesis and potential treatment of skin diseases. , 2004, Journal of the American Academy of Dermatology.

[28]  Yaping Liu,et al.  Capturing and profiling adult hair follicle stem cells , 2004, Nature Biotechnology.

[29]  E. Fuchs,et al.  Defining the Epithelial Stem Cell Niche in Skin , 2004, Science.

[30]  M. Omary,et al.  'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments. , 2002, Current opinion in cell biology.

[31]  E. Wright,et al.  Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? , 2001, Oncogene.

[32]  Y. Chai,et al.  Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF-beta-mediated epidermal homeostasis. , 2001, Developmental biology.

[33]  M. Martin,et al.  TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? , 2000, International journal of radiation oncology, biology, physics.

[34]  Nina Bhardwaj,et al.  Consequences of cell death: exposure to necrotic tumor cells , 2000 .

[35]  V. Reeve,et al.  Modulation of IL-10, IL-12, and IFN-gamma in the epidermis of hairless mice by UVA (320-400 nm) and UVB (280-320 nm) radiation. , 1999, The Journal of investigative dermatology.

[36]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[37]  R. Derynck,et al.  Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition , 1997 .

[38]  R. Derynck,et al.  Expression of a dominant-negative type II transforming growth factor beta (TGF-beta) receptor in the epidermis of transgenic mice blocks TGF-beta-mediated growth inhibition. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[39]  E. Fuchs,et al.  Programming gene expression in developing epidermis. , 1994, Development.

[40]  H. Moses,et al.  Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. , 1984, Science.