Promoting effect of lactoferrin on barrier function and epithelial differentiation of human keratinocytes.
The purpose of this study was to elucidate the effects of bovine lactoferrin on keratinocyte differentiation and barrier function. Addition of bovine lactoferrin to differentiating HaCaT human keratinocytes led to increased transepithelial electrical resistance (TER), a marker of epithelial barrier function. This elevation was followed by upregulation of two differentiation markers, involucrin and filaggrin. The expression level of sterol regulatory element-binding protein-1 was also enhanced by bovine lactoferrin. The lactoferrin-induced upregulation of involucrin and filaggrin expression were confirmed in normal human epidermal keratinocytes (NHEK). Treatment with SB203580, a p38 mitogen-activated protein kinase (MAPK) α inhibitor, impaired the upregulation of involucrin and filaggrin expression in response to lactoferrin. The elevation of p38 MAPK phosphorylation was further enhanced by lactoferrin in the initial stage of differentiation of HaCaT keratinocytes. The findings suggest that bovine lactoferrin promotes epithelial differentiation by a p38-MAPK-dependent mechanism.
a Functional Biomolecules Research Group, National Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.|b Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8572, Japan.
Ryo
R
Uchida
a Functional Biomolecules Research Group, National Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.
Reiji
R
Aoki
a Functional Biomolecules Research Group, National Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.|c Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Ayako
A
Aoki-Yoshida
b Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8572, Japan.
Atsushi
A
Tajima
a Functional Biomolecules Research Group, National Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan.
Yoshiharu
Y
Takayama
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000091344:Filaggrin Proteins; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011498:Protein Precursors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007093:Imidazoles; D007381:Intermediate Filament Proteins; D011498:Protein Precursors; D011725:Pyridines; C032253:involucrin; D048051:p38 Mitogen-Activated Protein Kinases; D007781:Lactoferrin; C093642:SB 203580
SREBP-1; filaggrin; filaggrine; involucrin; involucrine; p38 MAPK; p38 mitogen-activated protein kinase; résistance électrique transépithéliale; sterol regulatory element-binding protein-1; transepithelial electrical resistance