Tetsuya Kuhara1, Koji Yamauchi, Keiji Iwatsuki. 1. Food Science & Technology Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa, 228-8583, Japan. t_kuhara@morinagamilk.co.jp
Abstract
PURPOSE: Orally administered bovine lactoferrin (bLF) exerts an anti-inflammatory effect on hepatitis and colitis animal models. To investigate the mechanism underlying the action of bLF, we explored the expression of inflammation-related factors in the intestine of a hepatitis mouse model after the oral administration of bLF and in several human intestinal cell lines treated with bLF. METHODS: The effects of bLF on the expression of interleukin-11 (IL-11) and bone morphogenetic protein 2 (BMP2) in the intestinal mucosa of a hepatitis mouse model as well as in cell cultures of human intestinal epithelial cells, myofibroblasts, and monocytes were examined using the real-time reverse transcription polymerase chain reaction. Epithelial cells and myofibroblasts were also cocultured using transwells. bLF transport, and IL-11 and BMP2 induction, as well as the interactions between the two cell types, were then analyzed after bLF treatment. RESULTS: In vivo, oral bLF administration increased the production of IL-11 and BMP2 in intestinal specimens. In vitro, bLF only stimulated the production of IL-11 in human intestinal myofibroblasts; i.e., it had no effect on BMP2 production in any cell type. In the transwell cocultures, bLF passed through the epithelium and directly stimulated IL-11 production in the myofibroblasts on the basolateral side. The IL-11 produced in the myofibroblasts subsequently acted protectively on the epithelial cells of the coculture. CONCLUSIONS: bLF upregulated the activity of anti-inflammatory factors, such as IL-11, in the intestine of a hepatitis mouse model and human intestinal myofibroblasts.
PURPOSE: Orally administered bovinelactoferrin (bLF) exerts an anti-inflammatory effect on hepatitis and colitis animal models. To investigate the mechanism underlying the action of bLF, we explored the expression of inflammation-related factors in the intestine of a hepatitismouse model after the oral administration of bLF and in several human intestinal cell lines treated with bLF. METHODS: The effects of bLF on the expression of interleukin-11 (IL-11) and bone morphogenetic protein 2 (BMP2) in the intestinal mucosa of a hepatitismouse model as well as in cell cultures of human intestinal epithelial cells, myofibroblasts, and monocytes were examined using the real-time reverse transcription polymerase chain reaction. Epithelial cells and myofibroblasts were also cocultured using transwells. bLF transport, and IL-11 and BMP2 induction, as well as the interactions between the two cell types, were then analyzed after bLF treatment. RESULTS: In vivo, oral bLF administration increased the production of IL-11 and BMP2 in intestinal specimens. In vitro, bLF only stimulated the production of IL-11 in human intestinal myofibroblasts; i.e., it had no effect on BMP2 production in any cell type. In the transwell cocultures, bLF passed through the epithelium and directly stimulated IL-11 production in the myofibroblasts on the basolateral side. The IL-11 produced in the myofibroblasts subsequently acted protectively on the epithelial cells of the coculture. CONCLUSIONS: bLF upregulated the activity of anti-inflammatory factors, such as IL-11, in the intestine of a hepatitismouse model and human intestinal myofibroblasts.
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