Resistance of LPS-activated bone marrow derived macrophages to apoptosis mediated by dexamethasone

Yasmin Ohana Haim, Naamit Deshet Unger, Miriam C. Souroujon, Moshe Mittelman, Drorit Neumann

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

Glucocorticoids (GC) display pleiotropic effects on the immune system. Macrophages are a major target for GC action. Here we show that dexamethasone (DEX), a synthetic GC, decreased viability of naïve bone marrow-derived macrophages (BMDM), involving an apoptotic mechanism. Administration of DEX together with lipopolysaccharide (LPS) protected BMDM against DEX-mediated cell death, suggesting that activated BMDM respond to DEX differently than naïve BMDM. An insight to the molecular basis of LPS actions was provided by a 7 fold increase in mRNA levels of glucocorticoid receptor beta (GRβ), a GR dominant-negative splice variant which inhibits GRα's transcriptional activity. LPS did not inhibit all DEX-mediated effects on BMDM; DEX significantly reduced the percentage of BMDM expressing high levels of the cell surface markers F4/80 and CD11b and led to a decrease in macrophage inflammatory protein 1 alpha (MIP1-α) mRNA and protein levels. These two DEX-mediated effects were not prevented by LPS. Our finding that LPS did not reduce the DEX-induced elevation of glucocorticoid-induced leucine zipper (GILZ), a mediator of GCs anti-inflammatory actions, may provide an underlying mechanism. These findings enable a better understanding of clinical states, such as sepsis, in which macrophages are activated by endotoxins and treatment by GCs is considered.

اللغة الأصليةالإنجليزيّة
رقم المقال4323
دوريةScientific Reports
مستوى الصوت4
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 10 مارس 2014

ملاحظة ببليوغرافية

Funding Information:
This work was performed in partial fulfillment of the requirements for a Ph.D. degree by Yasmin Ohana Haim and by Naamit Deshet Unger at the Sackler Faculty of Medicine, Tel Aviv University, Israel. The project was supported by a grant from the Multiple Myeloma Research Foundation to D.N. and a grant from the Open University Research Authority to M.C.S.

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