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TGF-á REGULATES TLR EXPRESSION AND FUNCTION ON EPIDERMAL KERATINOCYTES.

Miller1, L.S., Sorensen1, O.E., Liu1, P.T., Jalian1, H.R., Eshtiaghpour1, D., Behmanesh1, B.E., Chung1, W., Starner2, T.D., Kim1, J., Sieling1, P.A., Ganz1, T., Modlin1, R.L. 1David Geffen School of Medicine, University of California, Los Angeles, California, 2Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Abstract

This study by researchers at the UCLA School of Medicine and the University of Iowa Hospitals and Clinics demonstrated that MatTek’s EpiDerm human skin tissue equivalent can be used to investigate how TGF-á, a growth and differentiation factor present during wound healing and in psoriasis, up-regulates toll-like receptor (TLR) expression and function on keratinocytes, thereby augmenting host defense mechanisms at epithelial surfaces. The expression of TLRs on epithelial cells provides a first line of defense against invading pathogens. Researchers at the David Geffen School of Medicine at UCLA and the University of Iowa Hospitals and Clinics (USA) investigated the regulated expression and function of TLR5 and TLR9 on human keratinocytes (EpiDerm human skin tissue equivalents), because they found by immunohistochemistry that these TLRs are expressed in distinct layers of the epidermis. The researchers found that TGF-á, 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-á regulated the function of TLR5 and TLR9 because activation with their respective ligands enhanced the production of IL-8 and human â-defensins. These findings provide evidence that TGF-á up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces.

Keywords

Bacterial flagellin, ELISA, EpiDerm, Host defense mechanisms, Human beta-defensins, IL-8, Immunohistochemistry, Psoriasis, RNA isolation, Real-time PCR, TLR5, TLR9, TLRs, Toll-like receptors, Wound Healing

Materials Tested

Bacterial flagellin, CpG 1826, CpG dinucleotides, TGF-a

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