Interleukin (IL)-6 modulates transforming growth factor-beta expression in skin and dermal fibroblasts from IL-6-deficient mice.

Interleukin (IL)-6 modulates transforming growth factor-beta expression in skin and dermal fibroblasts from IL-6-deficient mice.
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DOI:
10.1111/j.1365-2133.2009.09215.x
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发表时间:
2009-08
期刊:
The British journal of dermatology
影响因子:
--
通讯作者:
Gallucci RM
Gallucci RM
中科院分区:
其他
文献类型:
--
作者:
Luckett-Chastain LR;Gallucci RM

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Interleukin (IL-6) and transforming growth factor (TGF)-β have been shown to play a role in skin development and maintenance. 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. 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. 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. 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.
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