Promoting effect of lactoferrin on barrier function and epithelial differentiation of human keratinocytes

• Published in: Biochemistry and cell biology Vol. 95; no. 1; pp. 64 - 68
• Main Authors: Uchida, Ryo, Aoki, Reiji, Aoki-Yoshida, Ayako, Tajima, Atsushi, Takayama, Yoshiharu
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.02.2017; Canadian Science Publishing NRC Research Press
• Subjects: Animals; Anti-Infective Agents - pharmacology; Cattle; Cell Differentiation - drug effects; Cells; Cells, Cultured; Effects; Electric Impedance; Enzyme Inhibitors - pharmacology; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Health aspects; Humans; Imidazoles - pharmacology; Intermediate Filament Proteins - metabolism; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Lactoferrin - pharmacology; Lactoferrins; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Physiological aspects; Protein Precursors - metabolism; Proteins; Pyridines - pharmacology; Skin; involucrine; filaggrine; résistance électrique transépithéliale; SREBP-1; transepithelial electrical resistance; sterol regulatory element-binding protein-1; involucrin; p38 mitogen-activated protein kinase; filaggrin; p38 MAPK
• ISSN: 0829-8211; 1208-6002
• DOI: 10.1139/bcb-2016-0147

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.