IL-6 family cytokines, STAT3 activators, exhibit differential effects in a ligand-specific manner in podocytes

Abstract

[Background]

IL-6 family cytokines play protective roles in cardiomyocytes via STAT3 activation. Glomerular podocytes, as an important component of the kidney blood filtration, are terminally differentiated cells as well as cardiomyocytes. Although some studies have shown that STAT3 activation is associated with podocyte dysfunction, it remains unclear whether activated STAT3 exhibits differential functions depending on cytokines. The aim of this study is to assess the effects of IL-6 family cytokines/STAT3 signaling in podocytes.

[Methods and results]

To examine the pathophysiological relevance of IL-6 family cytokines in kidney diseases, C57BL/6J mice were subjected to ischemia-reperfusion or lipopolysaccharide (LPS) treatment. Quantitative PCR demonstrated that the expression level of IL-6, leukemia inhibitory factor (LIF) and IL-11 was upregulated in injured kidneys. In cultured podocytes, STAT3 was rapidly activated in response to the stimulation with IL-6, LIF or IL-11. Interestingly, LIF and IL-11 treatment suppressed H₂O₂-induced cell death in cultured podocytes, whereas IL-6 tended to increase cell death.

[Conclusion]

STAT3 could differentially function in an activator cytokine-specific manner, in podocytes, providing the important information for the development of therapy targeting STAT3 for kidney diseases.