AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine rel...AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.展开更多
NETosis is a regulated form of neutrophil cell death that contributes to the host defense against pathogens and was linked to various diseases soon after its first description in 2004.During NETosis,neutrophils releas...NETosis is a regulated form of neutrophil cell death that contributes to the host defense against pathogens and was linked to various diseases soon after its first description in 2004.During NETosis,neutrophils release neutrophil extracellular traps(NETs),which can capture and kill bacteria and other pathogens to prevent them from spreading.Although substantial progress has been made in our understanding of NETosis,the precise mechanism underlying NETosis is still a matter of debate.Research continues to elucidate the molecular pathways involved in NETosis.In recent years,interactions with the complement and coagulation systems have become increasingly apparent.Activated complement proteins can stimulate NET formation,and NETs,in turn,can serve as a platform for complement activation.In addition,NETs can act as a scaffold for thrombus formation during coagulation.While crosstalk between the coagulation and complement systems has been previously described,NETosis appears to be a third important player in this consortium to protect the host against pathogens.This review summarizes our current knowledge on the mutual interactions between NETosis,the complement system and the coagulation system,with an emerging description of their complex triangular relationship.展开更多
文摘AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
基金This work was supported in part by the Dutch Technology Foundation STW.
文摘NETosis is a regulated form of neutrophil cell death that contributes to the host defense against pathogens and was linked to various diseases soon after its first description in 2004.During NETosis,neutrophils release neutrophil extracellular traps(NETs),which can capture and kill bacteria and other pathogens to prevent them from spreading.Although substantial progress has been made in our understanding of NETosis,the precise mechanism underlying NETosis is still a matter of debate.Research continues to elucidate the molecular pathways involved in NETosis.In recent years,interactions with the complement and coagulation systems have become increasingly apparent.Activated complement proteins can stimulate NET formation,and NETs,in turn,can serve as a platform for complement activation.In addition,NETs can act as a scaffold for thrombus formation during coagulation.While crosstalk between the coagulation and complement systems has been previously described,NETosis appears to be a third important player in this consortium to protect the host against pathogens.This review summarizes our current knowledge on the mutual interactions between NETosis,the complement system and the coagulation system,with an emerging description of their complex triangular relationship.
