title: Bovine lactoferrin induces interleukin-11 production in a hepatitis mouse model and human intestinal myofibroblasts.
abstract: OBJECTIVE
  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.
authors.affiliation: Food Science & Technology Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa, 228-8583, Japan. t_kuhara@morinagamilk.co.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kuhara
authors.forename: Koji
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D002417:Cattle; D004195:Disease Models, Animal; D006505:Hepatitis / Q000188:drug therapy*; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D055396:Bone Morphogenetic Protein 2; D017370:Interleukin-11; D007781:Lactoferrin