The roles of NF-κB and ROS in regulation of pro-inflammatory mediators of inflammation induction in LPS-stimulated zebrafish embryos

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>In this study, the roles of reactive oxygen species (ROS) and NF-κB on inflammation induction in lipopolysaccharide (LPS)-stimulated zebrafish embryos were evaluated using N-acetyl-<SMALL>L</SMALL>-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), specific inhibitors of ROS and NF-κB, respectively. LPS-stimulated zebrafish embryos showed increasing production of NO and ROS and expression of iNOS and COX-2 protein, compared to a control group without LPS. However, NAC significantly inhibited production of NO and ROS and markedly suppressed expression of iNOS and COX-2 protein in LPS-stimulated zebrafish embryos. The mRNA expressions of NF-κB such as p65NF-κB and IκB-A were significantly increased after LPS stimulation, whereas PDTC attenuated mRNA expression of NF-κB. PDTC also inhibited production of NO and reduced expression of iNOS and COX-2 protein in LPS-stimulated zebrafish embryos. Taken together, these results indicated that LPS increases pro-inflammatory mediators in zebrafish embryos through ROS and NF-κB regulation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We confirmed the roles of ROS and NF-κB in LPS-stimulated zebrafish embryos. </LI> <LI> We employed NAC and PDTC, which are specific inhibitors of ROS and NF-kB. </LI> <LI> NAC inhibited LPS-induced NO and ROS production and iNOS and COX-2 expression. </LI> <LI> PDTC also inhibited LPS-induced NO production and iNOS and COX-2 expression. </LI> <LI> PDTC significantly inhibited LPS-induced increases in the mRNA expression of NF-κB. </LI> </UL> </P>