1. TGF-alpha regulates TLR expression and function on epidermal keratinocytes.
- Author
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Miller LS, Sørensen OE, Liu PT, Jalian HR, Eshtiaghpour D, Behmanesh BE, Chung W, Starner TD, Kim J, Sieling PA, Ganz T, and Modlin RL
- Subjects
- Adjuvants, Immunologic physiology, Animals, DNA-Binding Proteins biosynthesis, Diffusion Chambers, Culture, Epidermal Cells, Epidermis immunology, Epidermis metabolism, Humans, Interleukin-8 biosynthesis, Membrane Glycoproteins genetics, Mice, Mice, Inbred BALB C, Organ Culture Techniques, RNA, Messenger biosynthesis, Receptors, Cell Surface genetics, Recombinant Proteins pharmacology, Toll-Like Receptor 5, Toll-Like Receptor 9, Toll-Like Receptors, Up-Regulation genetics, Up-Regulation immunology, beta-Defensins biosynthesis, Keratinocytes immunology, Keratinocytes metabolism, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins physiology, Receptors, Cell Surface biosynthesis, Receptors, Cell Surface physiology, Transforming Growth Factor alpha physiology
- Abstract
The expression of TLRs on epithelial cells provides a first line of defense against invading pathogens. We investigated the regulated expression and function of TLR5 and TLR9 on human keratinocytes, because we found by immunohistochemistry that these TLRs are expressed in distinct layers of the epidermis. We found that TGF-alpha, a growth and differentiation factor that is present during wound healing and in psoriasis, increased the expression of both TLR5 and TLR9 on keratinocytes. In addition, TGF-alpha regulated the function of TLR5 and TLR9, because activation with their respective ligands enhanced the production of IL-8 and human beta-defensins. These findings provide evidence that TGF-alpha up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces.
- Published
- 2005
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