Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 P310

SFEBES2008 Poster Presentations Steroids (35 abstracts)

Characterisation of 11β-hydroxysteroid dehydrogenase type 1 in human ocular and orbital fibroblasts.

Ravi Vijapurapu 1 , Claire Onyimba 2 , Pamela Khosla 2 , Alexandra Sinclair 2 , John Curnow 1 , Elizabeth Walker 2 , Mark Cooper 2 & Saaeha Rauz 1


1Academic Unit of Ophthalmology, Division of Immunity and Infection and 2Division of Medical Sciences, Department of Endocrinology, University of Birmingham, Birmingham, UK.


Ocular and orbital tissues are extremely susceptible to damage by immune-mediated inflammatory conditions, such as thyroid-associated-ophthalmopathy (TAO). Recent studies have implicated fibroblasts in the development of chronic inflammation. Once activated by inflammatory cytokines, fibroblasts secrete pro-inflammatory cytokines perpetuating the inflammatory process, causing significant tissue damage. Synovial fibroblasts have been reported to regulate inflammation by increasing local cortisol production via oxo-reductase activity of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This study characterised the expression and activity of 11β-HSD1 in ocular fibroblasts and evaluated its regulation by pro- and anti-inflammatory cytokines.

Primary fibroblast cultures were developed from normal human conjunctival, corneal, scleral and orbital fat tissues (ethical approval obtained). 11β-HSD1 activity assays carried out following 24 h incubation with tumour necrosis factor-α (TNFα), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon-γ (IFNγ), and transforming growth factor-β (TGFβ), illustrated 11β-HSD1 oxo-reductase activity in fibroblasts from all four ocular tissues, with a significant induction in enzyme activity from TNFα-treated fibroblasts. Increased gene expression of 11β-HSD1, glucocorticoid receptor α (GRα), hexose-6-phosphate dehydrogenase (H6PDH), IL-6, TGFβ1, and interleukin 1β (IL-1β) was demonstrated in fibroblasts treated with TNFα and IL-6, by real-time PCR. Analysis of the culture supernatant by Multiplex ELISA, illustrated repression in the synthesis of pro-inflammatory cytokines (IL-6, IL-8, TNFα, and IFNγ), following the induction of 11β-HSD1.

This study has identified an increase in both expression and activity of 11β-HSD1 in response to pro-inflammatory cytokines. This demonstrates intrinsic regulation of inflammation by increasing cortisol levels within the stromal microenvironment. Consequently, this isozyme may be a potential therapeutic target in conditions such as TAO, due to its regulatory role in the control of inflammation.

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