title: Enhanced LPS-induced activation of IL-27 signalling in sarcoidosis.
abstract: Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood.
  
  
  
  Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects. Protein and mRNA (in PBMC) levels for IL-27 and IL-35 (IL27, EBI3, IL12A subunits) as well as IL-27 receptor (IL6ST and IL27RA subunits) were assessed spontaneously and following direct (LPS) and indirect (anti-CD3/28 activation beads) macrophage stimulation using RT- PCR, ELISA and flow cytometry.
  
  
  
  Following stimulation with LPS, PBMC of patients with sarcoidosis displayed significantly enhanced expression of IL27 and EBI3 mRNA (p = 0.020 and p = 0.037 respectively) compared to PBMCs from healthy controls. There was also significantly enhanced production of IL-27 by PBMC from patients with sarcoidosis compared to healthy controls in response to LPS stimulation (p = 0.027). IL6ST mRNA and IL6ST protein were significantly lower in patients with sarcoidosis (mRNA p = 0.0002; MFI p = 0.0015) whilst IL27RA protein levels were significantly higher in patients with sarcoidosis compared to healthy controls (MFI p < 0.0001). Plasma IL-35 protein levels did not differ between control and sarcoidosis subjects (p = 0.23).
  
  
  
  These results suggest there may be exaggerated activation of IL-27 signalling in response to LPS in sarcoidosis.
authors: Inflammation and Infection Research, School of Medical Sciences, Faculty of Medicine, UNSW Australia, NSW, Australia; Department of Respiratory Medicine, Prince of Wales' Hospital Clinical School, Prince of Wales' Hospital Sydney, NSW, Australia; Faculty of Medicine, University of Heidelberg, Germany. Electronic address: sringkowski@gmx.de.
authors: Sabine
authors: S
authors: Ringkowski
authors: Inflammation and Infection Research, School of Medical Sciences, Faculty of Medicine, UNSW Australia, NSW, Australia; Department of Respiratory Medicine, Prince of Wales' Hospital Clinical School, Prince of Wales' Hospital Sydney, NSW, Australia.
authors: Joshua
authors: J
authors: Loke
authors: Inflammation and Infection Research, School of Medical Sciences, Faculty of Medicine, UNSW Australia, NSW, Australia; Department of Respiratory Medicine, Prince of Wales' Hospital Clinical School, Prince of Wales' Hospital Sydney, NSW, Australia.
authors: Shuying
authors: S
authors: Huang
authors: Inflammation and Infection Research, School of Medical Sciences, Faculty of Medicine, UNSW Australia, NSW, Australia; Department of Respiratory Medicine, Prince of Wales' Hospital Clinical School, Prince of Wales' Hospital Sydney, NSW, Australia.
authors: Hasib
authors: H
authors: Ahmadzai
authors: Pneumology and Critical Care Medicine, Translational Lung Research Center Heidelberg (TLRCH), Member of the German Lung Research Foundation (DZL), University of Heidelberg, Germany.
authors: Felix J F
authors: FJ
authors: Herth
authors: Inflammation and Infection Research, School of Medical Sciences, Faculty of Medicine, UNSW Australia, NSW, Australia; Department of Respiratory Medicine, Prince of Wales' Hospital Clinical School, Prince of Wales' Hospital Sydney, NSW, Australia.
authors: Paul S
authors: PS
authors: Thomas
authors: Inflammation and Infection Research, School of Medical Sciences, Faculty of Medicine, UNSW Australia, NSW, Australia.
authors: Cristan
authors: C
authors: Herbert
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006099:Granuloma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018664:Interleukin-12 / Q000378:metabolism; D064094:Interleukin-27 / Q000378:metabolism*; D007378:Interleukins / Q000097:blood* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D012507:Sarcoidosis / Q000097:blood* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D016207:Cytokines; C494199:IL6ST protein, human; D007166:Immunosuppressive Agents; D064094:Interleukin-27; D007378:Interleukins; D008070:Lipopolysaccharides; C464565:MYDGF protein, human; D012333:RNA, Messenger; C532417:interleukin-35, human; D050822:Cytokine Receptor gp130; D018664:Interleukin-12; D007703:Peptidyl-Dipeptidase A
keywords: IL-27; IL-35; IL27RA; IL6ST; LPS; Sarcoidosis