title: Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis.
abstract: Rapid activation of adrenal steroid release plays a pivotal role in an organism's first line of defense during sepsis. Adrenal gland function is often suppressed in critically ill patients and negatively impacts the overall survival rate. Increasingly, experimental and clinical evidence suggests that Toll-like receptors (TLRs), components of the innate immune system, play a key role in the mediation of systemic responses to invading pathogens during sepsis. In the present study, we aimed to elucidate the effect of TLR2, TLR4 and CD14 upregulation on adrenocortical cell steroidogenesis. We found that TLR4 and CD14 but not TLR2 overexpression in NCI-H295R cells inhibited basal and acute cortisol and aldosterone production. This effect could be partially explained by reduced expression of enzymes involved in the synthesis of latter steroids--CYP11B1 and CYP11B2. Together, these data suggest that TLR upregulation in the steroid producing cells may be involved in the adrenal gland dysfunction during sepsis.
authors.affiliation: Department of Medicine III, Technical University Dresden, University of Technology, Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Waldemar.kanczkowski@uniklinikum-dresden.de
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kanczkowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Tymoszuk
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Volker
authors.initials: V
authors.lastname: Janitzky
authors.forename: Torsten
authors.initials: T
authors.lastname: Weirich
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.forename: Monika
authors.initials: M
authors.lastname: Ehrhart-Bornstein
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002999:Clone Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018950:Lipopolysaccharide Receptors; D013256:Steroids; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D002784:Cholesterol