“…However, there were no quantitative differences in cleaved caspase-1 between FANCC-deficient and control cells, indicating that the control point for the FA proteins was likely upstream of posttranslational IL-1b processing ( Figure 2C). Glyburide also unexpectedly 40 suppressed TLR-induced TNF-a production from wild-type and Fancc 2/2 BMDM ( Figure 1D). The mechanism for this result is unknown, but because this effect was only noted in murine BMDM and not in human cells, it may reflect a species-specific enhancement of TNF-a production by autocrine IL-1 receptor activation or an off-target effect of glyburide.…”
Section: Discussionmentioning
confidence: 88%
“…Although it has been shown that glyburide can reduce TNF-a expression in monocytes after LPS treatment of whole blood, this effect was not observed when isolated monocytes were treated. 40 We have previously shown that TNF-a production is inhibited by the p38 MAPK inhibitor BIRB 796. 17 IL-1b expression is also known to be controlled by a p38 MAPK-dependent pathway in macrophages, 28 and we confirmed that inhibition of p38 suppressed TLR-induced IL-1b overproduction by T-shFC cells and by FA patient CD14…”
“…However, there were no quantitative differences in cleaved caspase-1 between FANCC-deficient and control cells, indicating that the control point for the FA proteins was likely upstream of posttranslational IL-1b processing ( Figure 2C). Glyburide also unexpectedly 40 suppressed TLR-induced TNF-a production from wild-type and Fancc 2/2 BMDM ( Figure 1D). The mechanism for this result is unknown, but because this effect was only noted in murine BMDM and not in human cells, it may reflect a species-specific enhancement of TNF-a production by autocrine IL-1 receptor activation or an off-target effect of glyburide.…”
Section: Discussionmentioning
confidence: 88%
“…Although it has been shown that glyburide can reduce TNF-a expression in monocytes after LPS treatment of whole blood, this effect was not observed when isolated monocytes were treated. 40 We have previously shown that TNF-a production is inhibited by the p38 MAPK inhibitor BIRB 796. 17 IL-1b expression is also known to be controlled by a p38 MAPK-dependent pathway in macrophages, 28 and we confirmed that inhibition of p38 suppressed TLR-induced IL-1b overproduction by T-shFC cells and by FA patient CD14…”
“…Glibenclamide reduced proinflammatory cytokines in an ex vivo model of human endotoxinemia under hypoxemic conditions (Schmid et al, 2011). It was suggested that glibenclamide inhibition was dependent on P2X 7 receptor activation of monocytes by ATP-releasing erythrocytes during hypoxia.…”
“…References kines only at high concentrations (19). In support with this finding, recent in vivo studies indicate that glibenclamide also exerts antiinflammatory effects both in animal and human studies (11,20).…”
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