title: Phagocyte-specific S100A8/A9 is upregulated in primary Sjögren's syndrome and triggers the secretion of pro-inflammatory cytokines in vitro.
abstract: OBJECTIVE
  To determine the role of S100A8/A9 in the pathogenesis of primary Sjögren's syndrome (pSS).
  
  
  METHODS
  The serum levels of S100A8/A9 were determined in pSS patients and healthy controls by ELISA. The expression of S100A8/A9 in salivary glands was assessed by immunohistochemistry. The phenotype of S100A8+ and S100A9+ cells was identified using double immunofluorescence. The effects of S100A8/A9 on cytokine production by peripheral blood mononuclear cells (PBMCs) from pSS patients were determined in vitro by flow cytometry. The effects of pro-inflammatory cytokines on S100A8/A9 secretion were additionally investigated in vitro by ELISA in PBMCs from pSS patients and control subjects.
  
  
  RESULTS
  Serum levels of S100A8/A9 were significantly increased in pSS patients compared to healthy controls. The tissular expression of S100A8 and S100A9, identified in professional phagocytes (neutrophils, monocytes and plasmacytoid dendritic cells), was increased in the salivary glands of pSS patients and correlated with focus score. In vitro, recombinant S100A8/A9 increased the production of IL-1β, IL-6, TNF-α, IFN-γ, IL-10, IL-17A and IL-22 by PBMCs. The S100A8/A9-induced increase in TNF-α production in pSS patients was significant relative to controls. Furthermore, IL-1β, TNF-α, IL-6, and IL-17A stimulated release of S100A8/A9 from PBMCs in pSS patients.
  
  
  CONCLUSIONS
  S100A8/A9 is increased in pSS patients contributing to the in vitro increased production of pro-inflammatory cytokines. As such, S100A8/A9 in concert with other cytokines might contribute to the pathogenesis of pSS.
authors.affiliation: URPhyM-NARILIS, Université de Namur; and Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
authors.forename: Charles
authors.initials: C
authors.lastname: Nicaise
authors.affiliation: Department of Rheumatology, Hôpital Erasme and Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Weichselbaum
authors.affiliation: Department of Immunology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
authors.forename: Liliane
authors.initials: L
authors.lastname: Schandene
authors.affiliation: Department of Rheumatology, Hôpital Erasme and Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gangji
authors.affiliation: Department of Rheumatology, Hôpital Erasme and Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Dehavay
authors.affiliation: URPhyM-NARILIS, Université de Namur, Belgium.
authors.forename: Joanna
authors.initials: J
authors.lastname: Bouchat
authors.affiliation: URPhyM-NARILIS, Université de Namur, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Balau
authors.affiliation: Institute of Immunology, University of Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.affiliation: Department of Rheumatology, Hôpital Erasme and Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, Belgium. msoyfoo@ulb.ac.be.
authors.forename: Muhammad S
authors.initials: MS
authors.lastname: Soyfoo
mesh_terms: D040501:Calgranulin A / Q000097:blood / Q000378:metabolism*; D040502:Calgranulin B / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines