S100B up-regulates macrophage production of IL1β and CCL22 and influences severity of retinal inflammation

Jennifer Niven, Joseph Hoare, Debbie McGowan, Gayathri Devarajan, Shigeyoshi Itohara, Monique Gannagé, Peter Teismann, Isabel Crane

Research output: Contribution to journalArticle

11 Citations (Scopus)
4 Downloads (Pure)

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.

Original languageEnglish
Article numbere0132688
Number of pages20
JournalPloS ONE
Volume10
Issue number7
Early online date23 Jul 2015
DOIs
Publication statusPublished - 23 Jul 2015

Fingerprint

Macrophages
macrophages
Up-Regulation
inflammation
Inflammation
interleukin-1
Interleukin-1
mice
Real-Time Polymerase Chain Reaction
quantitative polymerase chain reaction
Infiltration
in vitro studies
bone marrow
Bone
Retinal Diseases
Histology
Flow cytometry
gene expression regulation
Gene Expression Regulation
Brain Diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

S100B up-regulates macrophage production of IL1β and CCL22 and influences severity of retinal inflammation. / Niven, Jennifer; Hoare, Joseph; McGowan, Debbie; Devarajan, Gayathri; Itohara, Shigeyoshi; Gannagé, Monique; Teismann, Peter; Crane, Isabel.

In: PloS ONE, Vol. 10, No. 7, e0132688, 23.07.2015.

Research output: Contribution to journalArticle

Niven, J, Hoare, J, McGowan, D, Devarajan, G, Itohara, S, Gannagé, M, Teismann, P & Crane, I 2015, 'S100B up-regulates macrophage production of IL1β and CCL22 and influences severity of retinal inflammation', PloS ONE, vol. 10, no. 7, e0132688. https://doi.org/10.1371/journal.pone.0132688
Niven, Jennifer ; Hoare, Joseph ; McGowan, Debbie ; Devarajan, Gayathri ; Itohara, Shigeyoshi ; Gannagé, Monique ; Teismann, Peter ; Crane, Isabel. / S100B up-regulates macrophage production of IL1β and CCL22 and influences severity of retinal inflammation. In: PloS ONE. 2015 ; Vol. 10, No. 7.
@article{637e2b309aea43259e50b3c020231bb8,
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.",
author = "Jennifer Niven and Joseph Hoare and Debbie McGowan and Gayathri Devarajan and Shigeyoshi Itohara and Monique Gannag{\'e} and Peter Teismann and Isabel Crane",
note = "Funding: This work was supported by funding awards to Dr Isabel Crane from the National Eye Research Centre, Bristol, UK (Grant ref. SCIAD 058); and NHS Grampian Endowment Trust (Grant ref. 10/16). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",
year = "2015",
month = "7",
day = "23",
doi = "10.1371/journal.pone.0132688",
language = "English",
volume = "10",
journal = "PloS ONE",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "7",

}

TY - JOUR

T1 - S100B up-regulates macrophage production of IL1β and CCL22 and influences severity of retinal inflammation

AU - Niven, Jennifer

AU - Hoare, Joseph

AU - McGowan, Debbie

AU - Devarajan, Gayathri

AU - Itohara, Shigeyoshi

AU - Gannagé, Monique

AU - Teismann, Peter

AU - Crane, Isabel

N1 - Funding: This work was supported by funding awards to Dr Isabel Crane from the National Eye Research Centre, Bristol, UK (Grant ref. SCIAD 058); and NHS Grampian Endowment Trust (Grant ref. 10/16). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2015/7/23

Y1 - 2015/7/23

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84941763603&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0132688

DO - 10.1371/journal.pone.0132688

M3 - Article

VL - 10

JO - PloS ONE

JF - PloS ONE

SN - 1932-6203

IS - 7

M1 - e0132688

ER -