Interleukin (IL)-10 attenuates lipopolysaccharide-induced IL-6 production via inhibition of IkappaB-zeta activity by Bcl-3.

The inhibitory effect of interleukin-10 (IL-10), an anti-inflammatory cytokine, on lipopolysaccharide (LPS)-induced IL-6 production was characterized by simultaneous stimulation of RAW 264.7 cells with LPS and IL-10. The presence of IL-10 significantly inhibited LPS-induced IL-6 production at a transcriptional level. The expression of IkappaB-zeta, which promotes IL-6 production, was induced in response to LPS and it was definitely suppressed in the presence of IL-10. Further, IL-10 inhibited LPS-induced NF-kappaB activation. A pharmacological inhibitor of NF-kappaB prevented LPS-induced IkappaB-zeta expression, suggesting that IL-10 might inhibit LPS-induced IkappaB-zeta expression via the inactivation of NF-kappaB. In LPS- and IL-10-stimulated cells, the expression of Bcl-3 that inhibits NF-kappaB activation was significantly augmented. Introduction of Bcl-3 siRNA abolished IL-10-mediated IkappaB-zeta inhibition. In the presence of Bcl-3, siRNA IL-10 failed to inhibit LPS-induced IL-6 production. Therefore, it was suggested that Bcl-3 induced by IL-10 might reduce LPS-induced IkappaB-zeta activity via inactivation of NF-kappaB and that reduced IkappaB-zeta activity failed to promote LPS-induced IL-6 production.