title: Interferon α2b increases MMP-13 and IL-10 expression in Kupffer cells through MAPK signaling pathways.
abstract: OBJECTIVE
  Kupffer cells play critical roles in both progression and resolution of liver fibrosis. Interferon α2b is an important immunoregulator which has anti-fibrotic effect in addition to its antiviral effect. It remained unclear whether the anti-fibrotic effect of interferon α2b is mediated by regulating functions of Kupffer cells.
  
  
  METHODS
  Primary isolated Kupffer cells were cultured with interferon α2b and the expression of matrix metalloproteinase-13, interleukin-10, transforming growth factor -β1 and tumor necrosis factor-α were measured. To investigate the role of mitogen-activated protein kinase pathways in regulating cytokines production by interferon α2b-stimulated Kupffer cells, inhibitors were given before cells were treated with interferon a2b.
  
  
  RESULTS
  Cell purity was more than 98%. Stimulating Kupffer cells with interferon α2b led to a dramatic increase in matrix metalloproteinase-13 and interleukin-10 expression. In contrast, the values of tumor necrosis factor-α and transforming growth factor -β1 remained unchanged throughout the 24-hour observation period. Inhibited ERK1/2 pathway prevented interferon α2b-triggered matrix metalloproteinase-13 production, while inhibited p38MAPK, ERK1/2 or JNK signaling pathways all blocked interleukin-10 expression.
  
  
  CONCLUSIONS
  Interferon α2b may exert anti-fibrotic effect by elevating the level of matrix metalloproteinase-13 and interleukin-10 in Kupffer cells, in a mitogen-activated protein kinase signaling pathways-dependent manner.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yu
authors.forename: Man
authors.initials: M
authors.lastname: Xie
authors.forename: Xu
authors.initials: X
authors.lastname: Fan
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005355:Fibrosis; D007155:Immunologic Factors / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D007728:Kupffer Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C556062:IL10 protein, mouse; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D048049:Extracellular Signal-Regulated MAP Kinases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse