COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy.
BACKGROUND
Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy.


OBJECTIVE
The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy.


METHODS
Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes.


METHODS
Clinic of Endocrinology, University Hospital, Malmö, Sweden.


METHODS
Patients in acute severe or in chronic phase of ophthalmopathy.


METHODS
Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac.


METHODS
Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes.


RESULTS
A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%.


CONCLUSIONS
We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.
Vondrichova
Tereza
T
Division of Diabetes and Endocrinology, Department of Clinical Sciences, Lund University, Malmö University Hospital, Malmö, Sweden.
de Capretz
Annika
A
Parikh
Hemang
H
Frenander
Christofer
C
Asman
Peter
P
Aberg
Magnus
M
Groop
Leif
L
Hallengren
Bengt
B
Lantz
Mikael
M
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D015870:Gene Expression; D049970:Graves Ophthalmopathy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D000077154:Rosiglitazone; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004008:Diclofenac; D003907:Dexamethasone; D013230:Stearoyl-CoA Desaturase; D051546:Cyclooxygenase 2