title: The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model.
abstract: BACKGROUND
  The exact mechanism of the inflammatory changes occurring during the development of Behçet's disease (BD) remains unclear.
  
  
  OBJECTIVE
  We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model.
  
  
  METHODS
  The classical vs. alternative activated macrophage ratio (M1/M2 ratio) was calculated by analyzing the surface markers CD16/32 and CD23 as M1 and M2 markers, respectively, by flow cytometry. mRNA expression of interferon (IFN)-γ and interleukin (IL)-6 as M1 and arginase-1, FIZZ-1, and MHC-II as M2 markers were analyzed by reverse transcription-polymerase chain reaction. Cytokine levels were assessed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The M1 phenotype was upregulated in BD mice, and an increased M1/M2 ratio was observed compared to that in asymptomatic BD normal and normal healthy mice. Recombinant (r)IFN-γ significantly increased the M1/M2 ratio (1.74±0.42) compared with that of rIL-4 (0.83±0.20). BD mice treated with rIL-4 showed a decreased M1/M2 ratio (1.2±0.3) compared to that of the rIFN-γ- (2.1±2.3) treated group and also showed ameliorated BD symptoms accompanied by downregulation of IL-17 and IL-6 and up-regulation of IL-4.
  
  
  CONCLUSIONS
  Therefore, modulation of macrophage phenotypes could be an effective therapeutic approach for treating BD in the future.
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Republic of Korea; Department of Biomedical Sciences, Ajou University Graduate School, Suwon 443-721, Republic of Korea.
authors.forename: A K M M
authors.initials: AK
authors.lastname: Anower
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Republic of Korea; Department of Biomedical Sciences, Ajou University Graduate School, Suwon 443-721, Republic of Korea.
authors.forename: Ju A
authors.initials: JA
authors.lastname: Shim
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Republic of Korea.
authors.forename: Bunsoon
authors.initials: B
authors.lastname: Choi
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Republic of Korea.
authors.forename: Hyuk Jae
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Republic of Korea; Department of Biomedical Sciences, Ajou University Graduate School, Suwon 443-721, Republic of Korea. Electronic address: sohnsh@ajou.ac.kr.
authors.forename: Seonghyang
authors.initials: S
authors.lastname: Sohn
mesh_terms: D000818:Animals; D001528:Behcet Syndrome / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D003078:Colchicine / Q000494:pharmacology; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology*; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010431:Pentoxifylline / Q000494:pharmacology; D010641:Phenotype; D018139:Simplexvirus / Q000472:pathogenicity*
chemical_list: D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma; D010431:Pentoxifylline; D003078:Colchicine
keywords: Behçet's disease; CD16/32 and CD23; Classical and alternative macrophages; Herpes simplex virus 1; Mouse model