Charles Nicaise1, Laura Weichselbaum2, Liliane Schandene3, Valérie Gangji2, Florence Dehavay2, Joanna Bouchat4, Benoît Balau4, Thomas Vogl5, Muhammad S Soyfoo6. 1. URPhyM-NARILIS, Université de Namur; and Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles, Belgium. 2. Department of Rheumatology, Hôpital Erasme and Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, Belgium. 3. Department of Immunology, Hôpital Erasme, Université Libre de Bruxelles, Belgium. 4. URPhyM-NARILIS, Université de Namur, Belgium. 5. Institute of Immunology, University of Münster, Germany. 6. Department of Rheumatology, Hôpital Erasme and Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, Belgium. msoyfoo@ulb.ac.be.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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: Fabiola Atzeni; Francesco Gozza; Giacomo Cafaro; Carlo Perricone; Elena Bartoloni Journal: Front Immunol Date: 2022-05-06 Impact factor: 8.786
Authors: Julius O Nyalwidhe; Wojciech J Grzesik; Tanya C Burch; Michele L Semeraro; Tayab Waseem; Ivan C Gerling; Raghavendra G Mirmira; Margaret A Morris; Jerry L Nadler Journal: PLoS One Date: 2017-09-06 Impact factor: 3.240