The molecular mechanisms underlying the inhibiting effects of lanthanum on lipopolysaccharide induced NF-κB activation

Objective To study the molecular mechanism of lanthanum on blocking lipopolysaccharide(LPS)-mediated activation of nuclear factor-kappaB (NF-κB)signaling in macrophages.Methods The RAW264.7 macrophages were cultured routinely and divided into 4 groups randomly:LaCl3 +LPS group,LPS group,LaCl3 group and control group.The nuclear translocation of p65 protein was detected by immunocytochemistry.Total,cytoplasmic and nuclear proteins were extracted respectively,and then the binding activity of p65 with the target gene was measured by ELISA.Western blot assays were also performed to detect the expression levels of the proteins,including nuclear p65,IκBα and IKK kinase,the phosphorylation status of IκBα and IKK kinase.Results Lanthanum can block LPS-induced activation of p65 protein through various ways,such as inhibiting its nuclear translocation,reducing its expression in the nuclei and decreasing its binding activity with the target genes.Lanthanum inhibited the degradation of LPS-induced IκBα,but the phosphorylation of LPS-induced IKKβ can not be blocked by lanthanum,nor did the phosphorylation ability of p-IKKβ on IκBα.Conclusion Lanthanum inhibited the degradation of IκBα,nuclei translocation of p65 protein and its binding activity with the target genes,thereby inhibited LPS-induced NFκB activation,which might be one of the inhibition mechanisms of lanthanum on nuclear activation. Key words: Lanthanum;  LPS;  NF-κB;  Macrophages