Transforming growth factor-beta/Smad3 signalling regulates inflammatory responses in a murine model of contact hypersensitivity

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http://hdl.handle.net/10138/240783

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Anthoni , M , Fyhrquist-Vanni , N , Wolff , H , Alenius , H & Lauerma , A 2008 , ' Transforming growth factor-beta/Smad3 signalling regulates inflammatory responses in a murine model of contact hypersensitivity ' , British Journal of Dermatology , vol. 159 , no. 3 , pp. 546-554 . https://doi.org/10.1111/j.1365-2133.2008.08696.x

Title: Transforming growth factor-beta/Smad3 signalling regulates inflammatory responses in a murine model of contact hypersensitivity
Author: Anthoni, M.; Fyhrquist-Vanni, N.; Wolff, H.; Alenius, H.; Lauerma, A.
Contributor: University of Helsinki, Finnish Institute of Occupational Health (TTL)
University of Helsinki, Haartman Institute (-2014)
University of Helsinki, Clinicum
Date: 2008-09
Language: eng
Number of pages: 9
Belongs to series: British Journal of Dermatology
ISSN: 0007-0963
URI: http://hdl.handle.net/10138/240783
Abstract: Background Transforming growth factor (TGF)-beta is an important modulator of immune functions and cellular responses, such as differentiation, proliferation, migration and apoptosis. The Smad proteins, which are intracellular TGF-beta signal transducers, mediate most actions of TGF-beta. Objectives This study examines the role of Smad3 in a murine model of contact hypersensitivity (CHS). Methods The CHS response to oxazolone was studied in Smad3-deficient mice. The ear swelling response was measured and skin biopsies from oxazolone-sensitized skin areas were obtained for RNA isolation, immunohistochemical analyses and histology. Ear draining lymph nodes were collected for RNA isolation and proliferation tests. Quantitative real-time polymerase chain reaction was used to quantify mRNA expression of cytokines, chemokines and transcription factors. Results The expression of proinflammatory [interleukin (IL)-1 beta, tumour necrosis factor-alpha, IL-6], Th2 (IL-4) and Th17 type cytokines (IL-17), as well as regulatory components (TGF-beta, Foxp3) increased significantly at the mRNA level in the skin of oxazolone-treated Smad3-/- mice when compared with wild-type controls. The expression of the Th1 type cytokine IFN-gamma and the chemokines CXCL9 and CXCL10 was, however, unaffected by the lack of Smad3. The number of neutrophils and expression of the chemokines CCL3 and CXCL5, which are both involved in neutrophil recruitment, were increased in mice lacking Smad3. Also Th2 type chemokines CCL24, CCL3 and CXCL5 were increased in the skin of Smad3-/- mice compared with wild-type mice. In the lymph nodes, mRNA of IL-1 beta and IL-17, but not IL-4, TGF-beta or Foxp3, was increased in Smad3-/- mice during the CHS response. Conclusions The lack of intact TGF-beta signalling via Smad3 results in an increased proinflammatory, Th2 and Th17 type response in the skin, as well as increased expression of regulatory elements such as TGF-beta and Foxp3. Understanding the role of Smad3 in the CHS response may offer treatment and prevention strategies in this often disabling disease.
Subject: chemokine
contact hypersensitivity
cytokine murine model
Smad3
transforming growth factor-beta
GROWTH-FACTOR-BETA
IL-17-PRODUCING T-CELLS
TGF-BETA
ATOPIC-DERMATITIS
TARGETED DISRUPTION
SKIN INFLAMMATION
FOXP3 EXPRESSION
IGE RESPONSE
SMAD3
MACROPHAGE
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