ZFIN ID: ZDB-PUB-160525-3
Glucocorticoid-induced attenuation of the inflammatory response in zebrafish
Chatzopoulou, A., Heijmans, J.P., Burgerhout, E., Oskam, N., Spaink, H.P., Meijer, A.H., Schaaf, M.J.
Date: 2016
Source: Endocrinology   157(7): 2772-84 (Journal)
Registered Authors: Meijer, Annemarie H., Schaaf, Marcel J. M., Spaink, Herman P.
Keywords: none
MeSH Terms:
  • Animals
  • Beclomethasone/pharmacology*
  • Beclomethasone/therapeutic use
  • Cell Movement/drug effects*
  • Gene Expression Profiling
  • Gene Expression Regulation/drug effects
  • Glucocorticoids/pharmacology*
  • Glucocorticoids/therapeutic use
  • Inflammation/drug therapy*
  • Macrophages/cytology
  • Macrophages/drug effects
  • Neutrophils/cytology
  • Neutrophils/drug effects
  • Receptors, Glucocorticoid/metabolism
  • Wound Healing/drug effects*
  • Zebrafish
PubMed: 27219276 Full text @ Endocrinology
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ABSTRACT
Glucocorticoids are steroid hormones that are secreted upon stress. Their effects are mediated by the glucocorticoid receptor (GR) which acts as a transcription factor. Since the anti-inflammatory activity of glucocorticoids has been well established, they are widely used clinically to treat many inflammatory and immune-related diseases. However, the exact specificity, mechanisms and level of regulation of different inflammatory pathways have not been fully elucidated. In the present study, a tail fin amputation assay was employed in 3-day-old zebrafish larvae to study the immunomodulatory effects of the synthetic glucocorticoid beclomethasone. First, a transcriptome analysis was performed, which showed that upon amputation mainly immune-related genes are regulated. This regulation was inhibited by beclomethasone for 86 of regulated genes. For two immune-related genes, tlr4bb and alox5ap, the amputation-induced increase was not attenuated by beclomethasone. Alox5ap is involved in eicosanoid biosynthesis, but the increase in LTB4 concentration upon amputation was abolished, and LXA4 levels were unaffected by beclomethasone. Furthermore, we studied the migration of neutrophils and macrophages towards the wound site. Our results show that amputation induced migration of both types of leukocytes, and that this migration was dependent on de novo protein synthesis. Beclomethasone treatment attenuated the migratory behavior of neutrophils in a GR-dependent manner, but left the migration of macrophages unaffected. In conclusion, beclomethasone has a dramatic inhibitory effect on the amputation-induced pro-inflammatory gene regulation, and this is reflected in an inhibition of the neutrophil migration, but not the migration of macrophages, which are likely to be involved in inflammation resolution.
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