title: S100B Up-Regulates Macrophage Production of IL1β and CCL22 and Influences Severity of Retinal Inflammation.
abstract: S100B is a Ca2+ binding protein and is typically associated with brain and CNS disorders. However, the role of S100B in an inflammatory situation is not clear. The aim of the study was to determine whether S100B is likely to influence inflammation through its effect on macrophages. A murine macrophage cell line (RAW 264.7) and primary bone marrow derived macrophages were used for in vitro studies and a model of retinal inflammatory disease in which pathogenesis is highly dependent on macrophage infiltration, Experimental Autoimmune Uveoretinitis, for in vitro study. Experimental Autoimmune Uveoretinitis is a model for the human disease posterior endogenous uveoretinitis, a potentially blinding condition, with an autoimmune aetiology, that mainly affects the working age group. To date the involvement of S100B in autoimmune uveoretinitis has not been investigated. Real-time PCR array analysis on RAW 246.7 cells indicated up-regulation of gene expression for various cytokines/chemokines in response to S100B, IL-1β and CCL22 in particular and this was confirmed by real-time PCR. In addition flow cytometry and ELISA confirmed up-regulation of protein production in response to S100B for pro-IL-1β and CCL22 respectively. This was the case for both RAW 264.7 cells and bone marrow derived macrophages. Induction of EAU with retinal antigen in mice in which S100B had been deleted resulted in a significantly reduced level of disease compared to wild-type mice, as determined by topical endoscopic fundus imaging and histology grading. Macrophage infiltration was also significantly reduced in S100B deleted mice. Real-time PCR analysis indicated that this was associated with reduction in CCL22 and IL-1β in retinas from S100B knock-out mice. In conclusion S100B augments the inflammatory response in uveoretinitis and this is likely to be, at least in part, via a direct effect on macrophages.
authors.affiliation: Division of Applied Medicine, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom; Division of Rheumatology and Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Niven
authors.affiliation: Division of Applied Medicine, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hoare
authors.affiliation: Division of Applied Medicine, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom.
authors.forename: Debbie
authors.initials: D
authors.lastname: McGowan
authors.affiliation: Division of Applied Medicine, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Devarajan
authors.affiliation: RIKEN Brain Science Institute, Wako, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Division of Rheumatology and Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Monique
authors.initials: M
authors.lastname: Gannagé
authors.affiliation: Division of Applied Medicine, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Teismann
authors.affiliation: Division of Applied Medicine, University of Aberdeen Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland, United Kingdom.
authors.forename: Isabel
authors.initials: I
authors.lastname: Crane
mesh_terms: D000818:Animals; D002460:Cell Line; D054422:Chemokine CCL22 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012173:Retinitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*; D014605:Uveitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse