May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Aqueous Humour Immunosuppressive Components Do Not Regulate Lipopolysaccharide Mediation of Autocrine Cortisol Bioavailability in Macrophage Subsets
Author Affiliations & Notes
  • V. Joganathan
    University of Birmingham, England, Birmingham, United Kingdom
    Academic unit of ophthalmology,
  • I. J. Bujalska
    University of Birmingham, England, Birmingham, United Kingdom
    Division of medical sciences,
  • A. Al-Hakami
    University of Birmingham, England, Birmingham, United Kingdom
    Academic unit of ophthalmology,
  • P. M. Stewart
    University of Birmingham, England, Birmingham, United Kingdom
    Division of medical sciences,
  • P. I. Murray
    University of Birmingham, England, Birmingham, United Kingdom
    Academic unit of ophthalmology,
  • S. Rauz
    University of Birmingham, England, Birmingham, United Kingdom
    Academic unit of ophthalmology,
  • G. R. Wallace
    University of Birmingham, England, Birmingham, United Kingdom
    Academic unit of ophthalmology,
  • Footnotes
    Commercial Relationships  V. Joganathan, None; I.J. Bujalska, None; A. Al-Hakami, None; P.M. Stewart, None; P.I. Murray, None; S. Rauz, None; G.R. Wallace, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 816. doi:https://doi.org/
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      V. Joganathan, I. J. Bujalska, A. Al-Hakami, P. M. Stewart, P. I. Murray, S. Rauz, G. R. Wallace; Aqueous Humour Immunosuppressive Components Do Not Regulate Lipopolysaccharide Mediation of Autocrine Cortisol Bioavailability in Macrophage Subsets. Invest. Ophthalmol. Vis. Sci. 2008;49(13):816. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The immune system has evolved to protect the individual from a wide variety of pathogens, but alongside this protective immunity there is frequently significant non-specific damage to the surrounding tissues. Glucocorticoids have potent immunosuppressive and anti-inflammatory properties and can be locally produced from circulating inactive cortisone by a tissue-specific regulating enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The aim of this study was to demonstrate cortisol generating capacity by human macrophage subsets and to elucidate its potential role as a mechanism contributing to ocular immune protection.

Methods: : CD14+ positive cells were isolated from human peripheral blood monocytes using MACS technique and cultured with cytokines GM-CSF or M-CSF to induce M1 and M2 macrophage populations respectively. Cultures were stimulated with Gram negative bacterial endotoxin, lipopolysaccharide (LPS), or tumour necrosis factor (TNF) in the presence or absence of known aqueous humour immunosuppressive components vasoactive intestinal peptide (VIP), transforming growth factorβ (TGF-β) and α-melanocyte stimulating hormone (α-MSH), and their effect on 11 β-HSD1 activity were determined.

Results: : M1 macrophages showed significant (p<0.001) up regulation of 11β-HSD1 activity (41.2±34.2%conversion/105 cells, mean±SEM, n=8) .By comparison, no 11β-HSD1 activity was seen in M2 cells. M1 11β-HSD1 activity was lost upon co-culture with LPS or TNF confirming that prolonged infective stimuli results in macrophage terminal differentiation and subsequent inability to generate cortisol locally. Ocular immunosuppressive components; VIP, TGF-β and α-MSH had no effect on 11β-HSD1 activity in M1 macrophages, following 8 hour incubation.

Conclusions: : We conclude that increased cortisol bioavailability secondary to up regulation of 11β-HSD1 enzyme following pathogenic stimuli in M1 macrophages in the intraocular microenvironment may contribute to ocular immune privilege.

Keywords: immune tolerance/privilege • corticosteroids • aqueous 
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