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10.1371/journal.pone.0171322 http://scihub22266oqcxt.onion/10.1371/journal.pone.0171322 C5313137!5313137!28207754     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+One 2017 ; 12 (2): ä Nephropedia Template TP {{tp|p=28207754|t=2017. Ascofuranone inhibits lipopolysaccharide?induced inflammatory response via NF-kappaB and AP-1, p-ERK, TNF-?, IL-6 and IL-1? in RAW 264 7 macrophages |pdf=|usr=}}{{28207754}} gab.com Text Ascofuranone inhibits lipopolysaccharide induced inflammatory response via NF-kappaB and AP-1, p-ERK, TNF- , IL-6 and IL-1 in RAW 264 7 macrophages JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28207754 #FOAvip The natural fungal compound ascofuranone (5-chloro-3-[(2E,6E)-7-[(2S)-5,5-dimethyl-4-oxo-tetrahydrofuran-2-yl]-3-methyl-oc ta-2,6-dienyl]-2,4-dihydroxy-6-methyl-benzaldehyde, MW 420.93) (AF) isolated from Ascochyta viciae has been known to promote cell cycle arrest and inhibit invasion of tumor cells. We have previously studied a structurally similar compound ascochlorin (ASC; MW 404.93) with regard to its anti-inflammatory activity in LPS- stimulated RAW 264.7 macrophages. In order to examine the relationship between the anti-inflammatory activities and the molecular differences between AF and ASC, the activity of AF is herein studied, because ASC has a unique trimethyl oxocyclohexyl structure, while AF has a unique dimethyl-oxo-tetrahydrofuran structure. AF dose-dependently inhibited the production of NO and iNOS and the COX-2 mRNA and protein levels in RAW 264.7 cells. In addition, AF suppressed mRNA expression levels of inflammatory cytokines such as TNF-?, IL-6, and IL-1?, as assessed by RT-PCR. AF (30?50 ?g/ml) treatment clearly inhibited the nuclear translocation of NF-?B, AP-1 (p-c-Jun) from the cytosolic space. Phosphorylation of I?B, which functions to maintain the activity of NF-?B, was decreased by AF treatment. Moreover, AF suppressed the binding of NF-?B (p65). Inhibition of IkBa phosphorylation and degradation inhibits nuclear translocation of p65. Immunofluorescence confocal microscopy analysis also revealed that translocation of NF-?B and AP-1 (p-c-Jun) was decreased upon AF treatment. AF specifically decreased the expression level of p-ERK, but not the expression level of p-p38 or p-JNK. Given these results, we suggest that AF suppresses the inflammatory response by targeting p-ERK. This indicates that AF is a negative regulator of LPS-stimulated nuclear translocation of NF-?B and AP-1 (p-c-Jun) in RAW 264.7 macrophages, and specifically it targets p-ERK. Therefore, AF and ASC exert their effects in different ways, most probably because their structural differences allow for specific recognition and inhibition of their target MAPKs. Our results further suggest that AF could be a natural bioactive compound useful for treating inflammation-mediated pathological diseases. Twit Text FOAVip Ascofuranone inhibits lipopolysaccharide induced inflammatory response via NF-kappaB and AP-1, p-ERK, TNF- , IL-6 and IL-1 in RAW 264 7 macrophages ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28207754 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28207754 #FOAvip English Wikipedia <ref>{{Cite pmid|28207754}}</ref> Ascofuranone inhibits lipopolysaccharide?induced inflammatory response via NF-kappaB and AP-1, p-ERK, TNF-?, IL-6 and IL-1? in RAW 264 7 macrophages #MMPMID28207754 Park JY; Chung TW; Jeong YJ; Kwak CH; Ha SH; Kwon KM; Abekura F; Cho SH; Lee YC; Ha KT; Magae J; Chang YC; Kim CH PLoS One 2017[]; 12 (2): ä PMID28207754show ga The natural fungal compound ascofuranone (5-chloro-3-[(2E,6E)-7-[(2S)-5,5-dimethyl-4-oxo-tetrahydrofuran-2-yl]-3-methyl-oc ta-2,6-dienyl]-2,4-dihydroxy-6-methyl-benzaldehyde, MW 420.93) (AF) isolated from Ascochyta viciae has been known to promote cell cycle arrest and inhibit invasion of tumor cells. We have previously studied a structurally similar compound ascochlorin (ASC; MW 404.93) with regard to its anti-inflammatory activity in LPS- stimulated RAW 264.7 macrophages. In order to examine the relationship between the anti-inflammatory activities and the molecular differences between AF and ASC, the activity of AF is herein studied, because ASC has a unique trimethyl oxocyclohexyl structure, while AF has a unique dimethyl-oxo-tetrahydrofuran structure. AF dose-dependently inhibited the production of NO and iNOS and the COX-2 mRNA and protein levels in RAW 264.7 cells. In addition, AF suppressed mRNA expression levels of inflammatory cytokines such as TNF-?, IL-6, and IL-1?, as assessed by RT-PCR. AF (30?50 ?g/ml) treatment clearly inhibited the nuclear translocation of NF-?B, AP-1 (p-c-Jun) from the cytosolic space. Phosphorylation of I?B, which functions to maintain the activity of NF-?B, was decreased by AF treatment. Moreover, AF suppressed the binding of NF-?B (p65). Inhibition of IkBa phosphorylation and degradation inhibits nuclear translocation of p65. Immunofluorescence confocal microscopy analysis also revealed that translocation of NF-?B and AP-1 (p-c-Jun) was decreased upon AF treatment. AF specifically decreased the expression level of p-ERK, but not the expression level of p-p38 or p-JNK. Given these results, we suggest that AF suppresses the inflammatory response by targeting p-ERK. This indicates that AF is a negative regulator of LPS-stimulated nuclear translocation of NF-?B and AP-1 (p-c-Jun) in RAW 264.7 macrophages, and specifically it targets p-ERK. Therefore, AF and ASC exert their effects in different ways, most probably because their structural differences allow for specific recognition and inhibition of their target MAPKs. Our results further suggest that AF could be a natural bioactive compound useful for treating inflammation-mediated pathological diseases. äAscofuranone inhibits lipopolysaccharide?induced inflammatory response(epmc).pdf DeepDyve Pubget Overpricing