Interleukin-1 beta induced activation of the hypothalamus-pituitary-adrenal axis is dependent on interleukin-1 receptors on non-hematopoietic cells
2014 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 40, 166-173 p.Article in journal (Refereed) Published
The proinflammatory cytokine interleukin-1 beta (IL-beta) plays a major role in the signal transduction of immune stimuli from the periphery to the central nervous system, and has been shown to be an important mediator of the immune-induced stress hormone release. The signaling pathway by which IL-1 beta exerts this function involves the blood-brain-barrier and induced central prostaglandin synthesis, but the identity of the blood-brain-barrier cells responsible for this signal transduction has been unclear, with both endothelial cells and perivascular macrophages suggested as critical components. Here, using an irradiation and transplantation strategy, we generated mice expressing IL-1 type 1 receptors (IL-1 RI) either in hematopoietic or non-hematopoietic cells and subjected these mice to peripheral immune challenge with IL-beta. Following both intraperitoneal and intravenous administration of IL-beta, mice lacking IL-1R1 in hematopoietic cells showed induced expression of the activity marker c-Fos in the paraventricular hypothalamic nucleus, and increased plasma levels of ACTH and corticosterone. In contrast, these responses were not observed in mice with IL-1R1 expression only in hematopoietic cells. Immunoreactivity for IL-1R1 was detected in brain vascular cells that displayed induced expression of the prostaglandin synthesizing enzyme cyclooxygenase-2 and that were immunoreactive for the endothelial cell marker CD31, but was not seen in cells positive for the brain macrophage marker CD206. These results imply that activation of the HPA-axis by IL-1 beta is dependent on IL-1R1 s on non-hematopoietic cells, such as brain endothelial cells, and that IL-1R1 on perivascular macrophages are not involved.
Place, publisher, year, edition, pages
Elsevier , 2014. Vol. 40, 166-173 p.
HPA-axis Corticosterone; ACTH c-Fos Paraventricular nucleus; Chimeric mice; Bone marrow transplantation; Brain endothelial cells; Perivascular macrophages; Cyclooxygenase-2
Clinical Medicine Cell and Molecular Biology Neurosciences
IdentifiersURN: urn:nbn:se:liu:diva-109874DOI: 10.1016/j.bbi.2014.03.015ISI: 000339458400019PubMedID: 24681250OAI: oai:DiVA.org:liu-109874DiVA: diva2:741612
Funding Agencies|Swedish Research Council [61X-078979]; Swedish Cancer Foundation [13 0295]; County Council of Ostergotland; JSPS [H24-451]2014-08-282014-08-282015-08-10