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10.1038/aps.2016.141 http://scihub22266oqcxt.onion/10.1038/aps.2016.141 C5342666!5342666 !28112185     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28112185 &cmd=llinks): Failed to open stream: HTTP request failed! 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LYRM03, an ubenimex derivative, attenuates LPS-induced acute lung injury in mice by suppressing the TLR4 signaling pathway |pdf=|usr=}}{{28112185 }} gab.com Text LYRM03, an ubenimex derivative, attenuates LPS-induced acute lung injury in mice by suppressing the TLR4 signaling pathway JO: Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=28112185 #FOAvip Toll-like receptor 4 (TLR4)-mediated signaling plays a critical role in sepsis-induced acute lung injury (ALI). LYRM03 (3-amino-2-hydroxy-4-phenyl-valyl-isoleucine) is a novel derivative of ubenimex, a widely used antineoplastic medicine. We previously found that LYRM03 has anti-inflammatory effects in cecal ligation puncture mouse model. In this study we determined whether LYRM03 attenuated LPS-induced ALI in mice. LPS-induced ALI mouse model was established by challenging the mice with intratracheal injection of LPS (5 mg/kg), which was subsequently treated with LYRM03 (10 mg/kg, ip). LYRM03 administration significantly alleviated LPS-induced lung edema, inflammatory cell (neutrophils and macrophages) infiltration and myeloperoxidase (MPO) activity, decreased pro-inflammatory and chemotactic cytokine (TNF-?, IL-6, IL-1?, MIP-2) generation and reduced iNOS and COX-2 expression in the lung tissues. In cultured mouse alveolar macrophages in vitro, pretreatment with LYRM03 (100 ?mol/L) suppressed LPS-induced macrophage activation by reducing Myd88 expression, increasing I?B stability and inhibiting p38 phosphorylation. These results suggest that LYRM03 effectively attenuates LPS-induced ALI by inhibiting the expression of pro-inflammatory mediators and Myd88-dependent TLR4 signaling pathways in alveolar macrophages. LYRM03 may serve as a potential treatment for sepsis-mediated lung injuries. Twit Text FOAVip LYRM03, an ubenimex derivative, attenuates LPS-induced acute lung injury in mice by suppressing the TLR4 signaling pathway ????Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=28112185 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28112185 #FOAvip English Wikipedia <ref>{{Cite pmid|28112185 }}</ref> LYRM03, an ubenimex derivative, attenuates LPS-induced acute lung injury in mice by suppressing the TLR4 signaling pathway #MMPMID28112185 He HQ ; Wu YX ; Nie YJ ; Wang J ; Ge M ; Qian F Acta Pharmacol Sin 2017[Mar]; 38 (3 ): 342-350 PMID28112185 show ga Toll-like receptor 4 (TLR4)-mediated signaling plays a critical role in sepsis-induced acute lung injury (ALI). LYRM03 (3-amino-2-hydroxy-4-phenyl-valyl-isoleucine) is a novel derivative of ubenimex, a widely used antineoplastic medicine. We previously found that LYRM03 has anti-inflammatory effects in cecal ligation puncture mouse model. In this study we determined whether LYRM03 attenuated LPS-induced ALI in mice. LPS-induced ALI mouse model was established by challenging the mice with intratracheal injection of LPS (5 mg/kg), which was subsequently treated with LYRM03 (10 mg/kg, ip). LYRM03 administration significantly alleviated LPS-induced lung edema, inflammatory cell (neutrophils and macrophages) infiltration and myeloperoxidase (MPO) activity, decreased pro-inflammatory and chemotactic cytokine (TNF-?, IL-6, IL-1?, MIP-2) generation and reduced iNOS and COX-2 expression in the lung tissues. In cultured mouse alveolar macrophages in vitro, pretreatment with LYRM03 (100 ?mol/L) suppressed LPS-induced macrophage activation by reducing Myd88 expression, increasing I?B stability and inhibiting p38 phosphorylation. These results suggest that LYRM03 effectively attenuates LPS-induced ALI by inhibiting the expression of pro-inflammatory mediators and Myd88-dependent TLR4 signaling pathways in alveolar macrophages. LYRM03 may serve as a potential treatment for sepsis-mediated lung injuries. |Acute Lung Injury/chemically induced/*drug therapy/immunology [MESH] |Animals [MESH] |Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use [MESH] |Cytokines/metabolism [MESH] |Inflammation/drug therapy/immunology/metabolism [MESH] |Lipopolysaccharides/*pharmacology [MESH] |Macrophage Activation/drug effects [MESH] |Male [MESH] |Mice, Inbred C57BL [MESH] |Neutrophil Infiltration/drug effects [MESH] |Oligopeptides/*therapeutic use [MESH] |Signal Transduction [MESH]LYRM03, an ubenimex derivative, attenuates LPS-induced acute lung inju(epmc).pdf DeepDyve Pubget Overpricing