title: Reversal of iC3b-inhibited dendritic cell differentiation via inhibition of the extracellular signal-regulated mitogen-activated protein kinase promotes CD4(+) T cell proliferation.
abstract: OBJECTIVE
  To investigate the roles of ERK1/2 and p38 MAPK cascades in the differentiation of iC3b-combined CD14(+) monocyte into CD1a(+) MDDC, and to study how these cells influence CD4(+) T cell proliferation.
  
  
  METHODS
  CD14(+) monocyte was co-cultured with iC3b with or without inhibitors specific for ERK1/2 or p38 MAPK pathways for 2days, then the expressions of CD14, CD1a, phophso-ERK1/2, phophso-p38, IL-10 and IL-12 p70 were detected, and CD4(+) T cell proliferation was measured via (3)H-TdR as well.
  
  
  RESULTS
  Maturation of CD1a(+) DC was inhibited by iC3b along with downregulated expressions of CD1a, phophso-p38 and IL-12p70 and upregulated expressions of phophso-ERK1/2 and IL-10, and the CD4(+) T cell proliferation was restrained accordingly. When pretreated with inhibitor specific for ERK1/2 pathway, the inhibited maturation of imDC was reversed prominently with a higher level expression of CD1a and IL-12p70, whereas expressions of phophso-ERK1/2 and IL-10 were lowered, and accordingly the CD4(+) T cell proliferation restored significantly.
  
  
  CONCLUSIONS
  iC3b inhibited the differentiation of CD14(+) monocytes into CD1a(+) MDDCs via ERK1/2 pathway, and restoration of CD1a(+) MDDCs maturation occurred with the treatment of inhibitors specific for ERK1/2 pathway. Meanwhile, treatment of the inhibitor for the ERK1/2 cascade reversed the inhibited CD4(+) T cell proliferation, implying a potential possibility for clinical intervention.
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Leng
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Luo
authors.forename: Kefei
authors.initials: K
authors.lastname: Kang
mesh_terms: D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D003179:Complement C3b / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D005434:Flow Cytometry; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D003179:Complement C3b; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases