Mechanism of LPS Induced IL-6 Expression in the Growth Arrested Human Mesanigial Cells

Jin, Dong Kyu

Abstract

Mesangial cell proliferation contributes to the development of glomerulonephritis and is associated with glomerulosclerosis. It has been reported that IL-6 is a pluri-potent cytokine which is involved in the mesangial inflammation and the activation of IL-6 is related to the recruitment of transcriptional factors or cytokines such as IL-1beta. It has been known that bacterial infection sometimes precedes the exacerbation of glomerulonephritis and bacterial LPS, a potent activator of IL-6, is presumed to be one of the mediators of this inflammatory process. To understand the underlying mechanisms of how IL-6 is activated by LPS, we examined the serial changes of the expression of IL-1beta, IL-6 and NF IL-6(nuclear factor for IL-6) using the growth arrested human mesangial cells at 0, 2, 4, 8, and 18 hours after LPS stimulation. Exposure of serum-free mesangial cells to LPS resulted in the production and the expression of IL-1beta and IL-6. However, there was a steady increase of IL-1b expression throughout the 18 hours, while the peak expression of IL-6 was around 4 hours after LPS stimulation and this peak expression of IL-6 was preceded by NF IL-6. Interestingly, the NF IL-6 expression was not observed in the IL-6 stimulation by r-IL-1beta stimulation. Furthermore, the addition of anti-IL-1beta prior to the LPS stimulation reduced the IL-6 expression partially, but, it did not affect the NF IL-6 expression. These results demonstrated that the mesangial IL-6 expression by LPS is mediated by NF IL-6 as well as IL-1beta in a separate pathways. The capacity of LPS to express IL-6 by these mechanisms may play a role in the mesangial inflammatory process.