title: Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23.
abstract: OBJECTIVE
  Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23.
  
  
  METHODS
  Peripheral blood monocyte isolated from 10 HLA-B27+patients and five HLA-B27+normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for seven days. Flow cytometry was used to detect monocyte purity and expression of macrophage markers. Analysis of mRNA expression for HLA-B and B27, UPR-associated proteins (BiP, CHOP, MDG1, and XBP1) and IL-23 was performed by RT-qPCR.
  
  
  RESULTS
  RT-qPCR data showed a significant overexpression of HLA-B27, UPR genes (BiP, CHOP, and XBP1), and IL-23 in M-CSF-derived macrophages from AS patients compared to healthy controls. Increased expression of MDG1 was not significant.
  
  
  CONCLUSIONS
  Our data suggest that UPR activation occurs in M-CSF-derived macrophages of AS patients and is accompanied by overexpression of HLA-B27. UPR appears to be associated with overproduction of IL-23 in AS macrophages.
authors.affiliation: a Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rezaiemanesh
authors.affiliation: b Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran , and.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: a Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|c Molecular Immunology Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Amirzargar
authors.affiliation: b Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran , and.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Vojdanian
authors.affiliation: b Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran , and.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Jamshidi
authors.affiliation: a Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.|c Molecular Immunology Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Nicknam
mesh_terms: D000328:Adult; D017209:Apoptosis; D005260:Female; D015796:HLA-B27 Antigen / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D013167:Spondylitis, Ankylosing / Q000276:immunology / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: D015796:HLA-B27 Antigen; D020381:Interleukin-17; D053759:Interleukin-23; D016173:Macrophage Colony-Stimulating Factor
keywords: Ankylosing spondylitis; HLA-B27; Interleukin-23; Macrophage; Unfolded protein response (UPR)