Role of the endothelial-derived endogenous anti-inflammatory factor Del-1 in inflammation-mediated adrenal gland dysfunction.
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.
Department of Internal Medicine III, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. waldemar.kanczkowski@uniklinikum-dresden.de
Waldemar
W
Kanczkowski
Antonios
A
Chatzigeorgiou
Sylvia
S
Grossklaus
David
D
Sprott
Stefan R
SR
Bornstein
Triantafyllos
T
Chavakis
D000307:Adrenal Gland Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D013312:Stress, Physiological; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone