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10.1111/bph.12998 http://scihub22266oqcxt.onion/10.1111/bph.12998 C4337697!4337697!25363690     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Pharmacol 2015 ; 172 (5): 1222-36 Nephropedia Template TP {{tp|p=25363690|t=2015. MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis |pdf=|usr=}}{{25363690}} gab.com Text MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25363690 #FOAvip Background and Purpose: MLN4924 prevents the formation of active cullin-RING ubiquitin ligase complexes and thus inhibits NF-?B signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs). Experimental Approach: Monocytes and DCs were challenged with TNF or LPS in the presence and absence of MLN4924. The effects of MLN4924 on cellular viability, pro-inflammatory gene induction and DC maturation were investigated using the MTT assay, elisa and FACS analysis. Mechanisms of cell death induction were evaluated by using inhibitors of caspases, RIPK1 and MLKL. Key Results: MLN4924 inhibited NF-?B activation and sensitized monocytes and immature DCs (iDCs) for TNFR1-induced cell death. Neither the caspase inhibitor zVAD-fmk, the RIPK1 inhibitor necrostatin-1 (nec-1) nor the MLKL inhibitor necrosulfonamide (NSA) alone prevented TNF-induced cell death. A combination of zVAD-fmk and nec-1 or NSA, however, rescued monocytes and iDCs from MLN4924/TNF-induced cell death indicating that MLN4924 affects anti-apoptotic and anti-necrotic activities in TNFR1 signalling. MLN4924 also converted the response of iDCs to LPS from maturation to cell death. LPS-induced cell death in MLN4924-treated iDCs was again only effectively blocked by cotreatment with zVAD-fmk and nec-1 or NSA. Noteworthy, MLN4924/LPS-induced cell death was almost completely independent of endogenous TNF. MLN4924 also strongly inhibited maturation and activation of iDCs that were rescued from cell death by zVAD-fmk and nec-1. Conclusions and Implications: Our data reveal a strong dual suppressive effect of MLN4924 on DC activity. The targeting of NAE by MLN4924 could be a new way to treat inflammatory diseases. Twit Text FOAVip MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25363690 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25363690 #FOAvip English Wikipedia <ref>{{Cite pmid|25363690}}</ref> MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis #MMPMID25363690 El-Mesery M; Seher A; Stühmer T; Siegmund D; Wajant H Br J Pharmacol 2015[Mar]; 172 (5): 1222-36 PMID25363690show ga Background and Purpose: MLN4924 prevents the formation of active cullin-RING ubiquitin ligase complexes and thus inhibits NF-?B signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs). Experimental Approach: Monocytes and DCs were challenged with TNF or LPS in the presence and absence of MLN4924. The effects of MLN4924 on cellular viability, pro-inflammatory gene induction and DC maturation were investigated using the MTT assay, elisa and FACS analysis. Mechanisms of cell death induction were evaluated by using inhibitors of caspases, RIPK1 and MLKL. Key Results: MLN4924 inhibited NF-?B activation and sensitized monocytes and immature DCs (iDCs) for TNFR1-induced cell death. Neither the caspase inhibitor zVAD-fmk, the RIPK1 inhibitor necrostatin-1 (nec-1) nor the MLKL inhibitor necrosulfonamide (NSA) alone prevented TNF-induced cell death. A combination of zVAD-fmk and nec-1 or NSA, however, rescued monocytes and iDCs from MLN4924/TNF-induced cell death indicating that MLN4924 affects anti-apoptotic and anti-necrotic activities in TNFR1 signalling. MLN4924 also converted the response of iDCs to LPS from maturation to cell death. LPS-induced cell death in MLN4924-treated iDCs was again only effectively blocked by cotreatment with zVAD-fmk and nec-1 or NSA. Noteworthy, MLN4924/LPS-induced cell death was almost completely independent of endogenous TNF. MLN4924 also strongly inhibited maturation and activation of iDCs that were rescued from cell death by zVAD-fmk and nec-1. Conclusions and Implications: Our data reveal a strong dual suppressive effect of MLN4924 on DC activity. The targeting of NAE by MLN4924 could be a new way to treat inflammatory diseases. äMLN4924 sensitizes monocytes and maturing dendritic cells for TNF-depe(epmc).pdf DeepDyve Pubget Overpricing