Impaired adrenal stress response in Toll-like receptor 2-deficient mice

被引:82
作者
Bornstein, SR [1 ]
Zacharowski, P
Schumann, RR
Barthel, A
Tran, N
Papewalis, C
Rettori, V
McCann, SM
Schulze-Osthoff, K
Scherbaum, WA
Tarnow, J
Zacharowski, K
机构
[1] Tech Univ Dresden, Carl Gustav Carus Univ Hosp, Dept Med, D-013071 Dresden, Germany
[2] Univ Dusseldorf, Dept Endocrinol Diabet & Rheumatol, D-40225 Dusseldorf, Germany
[3] Univ Dusseldorf, Dept Anaesthesiol, D-40225 Dusseldorf, Germany
[4] Univ Dusseldorf, Dept Mol Med, D-40225 Dusseldorf, Germany
[5] Consejo Nacl Invest Cient & Tecn, Ctr Estudios Farmacol & Bot, RA-1414 Buenos Aires, DF, Argentina
[6] German Diabet Inst, D-40225 Dusseldorf, Germany
[7] Humboldt Univ, Charite Univ Med Ctr, Inst Microbiol & Hyg, D-10117 Berlin, Germany
[8] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA
关键词
endotoxemia; inflammation; glucocorticoids; immune response;
D O I
10.1073/pnas.0407550101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Septicemia is one of the major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. The family of Toll-like receptors(TLRs) is critical in the early immune response upon bacterial infection, and TLR polymorphisms are frequent in humans. Here, we demonstrate that TLR-2 deficiency in mice is associated with reduced plasma corticosterone levels and marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have an impaired adrenal corticosterone release after inflammatory stress induced by bacterial cell wall compounds. This defect appears to be mediated by a decrease in systemic and intraadrenal cytokine expression, including IL-1, tumor necrosis factor alpha, and IL-6. Our data demonstrate a link between the innate immune system and the endocrine stress response. The critical role of TLR-2 in adrenal glucocorticoid regulation needs to be considered in patients with inflammatory disease.
引用
收藏
页码:16695 / 16700
页数:6
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