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Interleukin (IL)‐6 modulates transforming growth factor‐β expression in skin and dermal fibroblasts from IL‐6‐deficient mice
Author(s) -
LuckettChastain L.R.,
Gallucci R.M.
Publication year - 2009
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2009.09215.x
Subject(s) - transforming growth factor , mapk/erk pathway , dermis , signal transduction , interleukin , cytokine , transforming growth factor beta , fibroblast , kinase , dermal fibroblast , microbiology and biotechnology , protein kinase a , tgf beta receptor 2 , biology , receptor , endocrinology , medicine , tgf alpha , immunology , growth factor , cell culture , anatomy , genetics
Summary Background Interleukin (IL‐6) and transforming growth factor (TGF)‐β have been shown to play a role in skin development and maintenance. Objectives A link between these two cytokines has yet to be identified and therefore in this study we investigated the modulation of TGF‐β1 and TGF‐β type 2 receptor (TGF‐βR2) by IL‐6 in skin. Methods An IL‐6 knockout (IL‐6KO) fibroblast‐populated lattice model and intradermal injections of IL‐6 into unwounded IL‐6KO mice were used to investigate the direct effects of IL‐6 treatment on TGF‐β and TGF‐βR2 expression and to determine the signalling mechanism. In addition, IL‐6KO and C57BL/6 control mice were wounded by a 4‐mm punch biopsy to monitor expression of TGF‐β1 and TGF‐βR2 within a wound over time. The expression of TGF‐β1 and TGF‐βR2 was assessed by real‐time quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay and immunohistology. Results Recombinant IL‐6 treatment of IL‐6KO lattices and intradermal injections of IL‐6 showed a significant induction of TGF‐β1 mRNA and protein, with TGF‐β1 expression localized in the dermis, while TGF‐βR2 expression was primarily in the epidermis in IL‐6KO mice. During healing, the expression of TGF‐β1 and TGF‐βR2 mRNA was significantly greater in unwounded and 7‐day‐old wounds from wild‐type mice; however, protein expression did not differ. Treatment with signal transduction inhibitors indicated that IL‐6 modulates TGF‐β through a mitogen‐activated protein kinase/extracellular signal‐regulated kinase (Mapk/Erk)‐dependent mechanism. Conclusion These studies indicate that IL‐6 has the ability to modulate the expression of TGF‐β and TGF‐βR2 to varying degrees in the skin, which may provide a possible mechanism for defining the role of IL‐6 in skin maintenance and a new association of IL‐6 with TGF‐β in pathologies associated with fibrosis.