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Endocrinology. 2013 Mar;154(3):1181-9. doi: 10.1210/en.2012-1617. Epub 2013 Jan 30.

Role of the endothelial-derived endogenous anti-inflammatory factor Del-1 in inflammation-mediated adrenal gland dysfunction.

Author information

1
Department of Internal Medicine III, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. waldemar.kanczkowski@uniklinikum-dresden.de

Abstract

Inflammation in the course of systemic inflammatory response syndrome (SIRS) or sepsis often results in dysregulation of the hypothalamic-pituitary-adrenal axis; however, the underlying mechanisms are not well understood. The adrenal gland is highly vascularized; thus, we hypothesized that endothelial dysfunction may actively participate in inflammation-related adrenal insufficiency. To address this hypothesis, we used the properties of developmental endothelial locus-1 (Del-1), which is an endothelial-derived anti-inflammatory factor that antagonizes integrin-dependent leukocyte adhesion. Here we identified that Del-1 is expressed in the adrenal gland and that its expression was down-regulated upon SIRS induction by systemic lipopolysaccharide administration. Furthermore, we observed increased leukocyte accumulation, inflammation, and higher apoptosis in the adrenal glands of Del-1-deficient mice as compared with wild-type mice. Strikingly, Del-1 deficiency was also associated with reduced corticosterone and ACTH levels 24 hours after lipopolysaccharide administration. Together, these data suggest that Del-1 may act as a gatekeeper of adrenal gland inflammation and may regulate the integrity of the hypothalamic-pituitary-adrenal axis stress response, thereby modulating adrenal (dys)function in the course of SIRS.

PMID:
23364949
DOI:
10.1210/en.2012-1617
[Indexed for MEDLINE]

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