Bovine β-Casein (1−28), a Casein Phosphopeptide, Enhances Proliferation and IL-6 Expression of Mouse CD19+Cells via Toll-like Receptor 4

Abstract

This study was conducted to elucidate the target cells and receptors which participate in the mitogenic and interleukin (IL)-6-enhancing effect of bovine β-casein (1−28), a casein phosphopeptide. When the spleen lymphocyte subset (CD4⁺, CD8⁺, and CD19⁺ cells) from C3H/HeN mice was cultured with the β-casein (1−28), it exerted a dose-dependent mitogenic effect on CD19⁺ cells. The effect of β-casein (1−28) was not apparent in the case of CD19⁺ cells from C3H/HeJ mouse. In addition, the effect was significantly inhibited by treating the C3H/HeN mouse-derived CD19⁺ cells with neutralizing antibody for toll-like receptor 4 (TLR4). Reverse transcription-polymerase chain reaction analysis showed that the β-casein (1−28) exerted an IL-6-enhancing effect on the CD19⁺ cells. The effect was also abrogated in either C3H/HeJ mouse-derived CD19⁺ cell culture or the anti-TLR4 antibody-added culture. These results suggest that the β-casein (1−28) stimulates both proliferation and IL-6 expression of CD19⁺ cells via TLR4. Keywords: Casein phosphopeptide; milk; mitogenic activity; CD19⁺ cells; IL-6; toll-like receptor 4