Triggering receptor expressed on myeloid Cells-2 (TREM2) inhibits steroidogenesis in adrenocortical cell by macrophage-derived exosomes in lipopolysaccharide-induced septic shock
Autor: | ShiYue Yang, Yaqi Sun, QiXing Chen, Shuijing Wu, Xiangming Fang, Hui Ye, Ruoqiong Huang, Ping Fang, Qian Zhai |
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Rok vydání: | 2021 |
Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_specialty Lipopolysaccharide Corticotropin-Releasing Hormone 030209 endocrinology & metabolism Inflammation Adrenocorticotropic hormone Exosomes Biochemistry Exosome 03 medical and health sciences chemistry.chemical_compound Corticotropin-releasing hormone 0302 clinical medicine Endocrinology Adrenocorticotropic Hormone Corticosterone Internal medicine medicine Animals Lactic Acid Receptors Immunologic Molecular Biology Membrane Glycoproteins Adrenal gland Septic shock Macrophages medicine.disease Shock Septic Survival Analysis Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Adrenal Cortex Steroids medicine.symptom |
Zdroj: | Molecular and Cellular Endocrinology. 525:111178 |
ISSN: | 0303-7207 |
Popis: | Purpose Endogenously produced glucocorticoids exhibit immunomodulating properties and are of pivotal importance for sepsis outcome. Uncontrolled activation of the immune-adrenal crosstalk increases the risk of sepsis-related death. Triggering receptor expressed on myeloid cells-2 (TREM2) is richly expressed on macrophages and has been demonstrated to improve outcome of sepsis by enhancing elimination of pathogens. However, the role and mode of action of macrophage TREM2 on adrenocortical steroidogenesis remains unclear in septic shock. Methods The acute septic shock model was established by intraperitoneally challenging wild-type (WT) and TREM2 knock-out (Trem2−/−) mice with lipopolysaccharide (LPS, 30 mg/kg). The mice were assessed for TREM2 expression and local inflammation in adrenal gland and for synthesis of corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in vivo. Bone marrow-derived macrophages or macrophage-derived exosomes were isolated from WT and Trem2−/− mice and were co-cultured with adrenocortical cells. The expression of steroidogenic enzymes and corticosterone production was assessed. Results Genetic deficiency of TREM2 caused significantly higher corticosterone levels at the early stage of LPS-induced septic shock; whereas TREM2 deficiency neither increased CRH and ACTH nor exacerbated the inflammation in adrenocortical tissue during septic shock. Ex vivo study revealed that Trem2−/− macrophages significantly promoted the expression of steroidogenic enzymes and increased production of corticosterone. Furthermore, Trem2−/− macrophage-derived exosomes were able to mimic Trem2−/− macrophages in enhancing adrenocortical steroidogenesis. Conclusions At the early stage of LPS-induced septic shock, corticosterone biosynthesis can be inhibited by macrophage TREM2 in adrenocortical cells, which might partially associate with macrophage-derived exosomes. |
Databáze: | OpenAIRE |
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