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COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy

Planck, Tereza LU ; de Capretz, Annika; Parikh, Hemang LU ; Frenander, Christofer LU ; Åsman, Peter LU ; Åberg, Magnus LU ; Groop, Leif LU ; Hallengren, Bengt LU and Lantz, Mikael LU (2007) In Thyroid 17(6). p.511-517
Abstract
Context: 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. Design: 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. Setting: Clinic of Endocrinology, University Hospital, Malmo, Sweden. Participants: Patients in acute severe or in chronic phase of ophthalmopathy. Interventions: Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In... (More)
Context: 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. Design: 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. Setting: Clinic of Endocrinology, University Hospital, Malmo, Sweden. Participants: Patients in acute severe or in chronic phase of ophthalmopathy. Interventions: Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Main outcome measure: 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%. Conclusion: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Thyroid
volume
17
issue
6
pages
511 - 517
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000247799500004
  • scopus:34447515451
ISSN
1557-9077
DOI
10.1089/thy.2007.0028
language
English
LU publication?
yes
id
99a75bb0-3372-4c06-9815-8b50f5020f7e (old id 648621)
date added to LUP
2007-12-19 13:38:59
date last changed
2017-08-20 04:16:29
@article{99a75bb0-3372-4c06-9815-8b50f5020f7e,
  abstract     = {Context: 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. Design: 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. Setting: Clinic of Endocrinology, University Hospital, Malmo, Sweden. Participants: Patients in acute severe or in chronic phase of ophthalmopathy. Interventions: Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Main outcome measure: 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%. Conclusion: 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.},
  author       = {Planck, Tereza and de Capretz, Annika and Parikh, Hemang and Frenander, Christofer and Åsman, Peter and Åberg, Magnus and Groop, Leif and Hallengren, Bengt and Lantz, Mikael},
  issn         = {1557-9077},
  language     = {eng},
  number       = {6},
  pages        = {511--517},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Thyroid},
  title        = {COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy},
  url          = {http://dx.doi.org/10.1089/thy.2007.0028},
  volume       = {17},
  year         = {2007},
}