Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis.

Waldemar Kanczkowski (1) , Piotr Tymoszuk (1) , Triantafyllos Chavakis (1) , Volker Janitzky (2) , Torsten Weirich (2) , Kai Zacharowski , Monika Ehrhart-Bornstein (1) , Stefan R. Bornstein (1)

1 Department of Medicine III
2 Department of Urology

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.

Mots clés: pattern recognition receptors

Mots clés: Adrenal insufficiency; adrenal dysfunction; steroidogenesis; immune-adrenal crosstalk; pattern recognition receptors.

Domaines: Biochimie, Biologie Moléculaire

Waldemar Kanczkowski, Piotr Tymoszuk, Triantafyllos Chavakis, Volker Janitzky, Torsten Weirich, et al.. Upregulation of TLR2 and TLR4 in the human adrenocortical cells differentially modulates adrenal steroidogenesis.. Molecular and Cellular Endocrinology, 2011, ⟨10.1016/j.mce.2010.12.013⟩. ⟨hal-00675793⟩