TGF-alpha regulates TLR expression and function on epidermal keratinocytes.
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.
Miller
Lloyd S
LS
Division of Dermatology, Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Sørensen
Ole E
OE
Liu
Philip T
PT
Jalian
H Ray
HR
Eshtiaghpour
Deborah
D
Behmanesh
Behnaz E
BE
Chung
Woosin
W
Starner
Timothy D
TD
Kim
Jenny
J
Sieling
Peter A
PA
Ganz
Tomas
T
Modlin
Robert L
RL
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015194:Diffusion Chambers, Culture; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D016211:Transforming Growth Factor alpha / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495346:TLR5 protein, human; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D016211:Transforming Growth Factor alpha; D023083:beta-Defensins