Mechanisms of the proinflammatory response of endothelial cells to Candida albicans infection.
Endothelial cells can influence significantly the host inflammatory response against blood-borne microbial pathogens. Previously, we found that endothelial cells respond to in vitro infection with Candida albicans by secreting interleukin 8 (IL-8) and expressing E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). We have now examined the mechanisms mediating this endothelial cell response. We determined that C. albicans stimulated endothelial cells to synthesize tumor necrosis factor alpha (TNF-alpha), which in turn induced these infected cells to secrete IL-8 and express E-selectin by an autocrine mechanism. Expression of VCAM-1 was mediated not only by TNF-alpha but also by IL-1alpha and IL-1beta, all of which were synthesized by endothelial cells in response to C. albicans. These three cytokines remained primarily cell associated rather than being secreted. Candidal induction of ICAM-1 expression was independent of TNF-alpha, IL-1alpha, and IL-1beta. These observations demonstrate that different proinflammatory endothelial cell responses to C. albicans are induced by distinct mechanisms. A clear understanding of these mechanisms is important for therapeutically modulating the endothelial cell response to C. albicans and perhaps other opportunistic pathogens that disseminate hematogenously.
Orozco
A S
AS
St. John's Cardiovascular Research Center, Division of Infectious Diseases, Department of Internal Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA.
Zhou
X
X
Filler
S G
SG
D002176:Candida albicans / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007375:Interleukin-1 / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D007375:Interleukin-1; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1