IL6 is an important cytokine which exerts significant impact on anti-infectious immunity of biological organism and tissue wound healing. Its abnormal secretion is closely related to many diseases, such as caner, diabetes and rheumatic arthritis. Dr. Nan Jing from school of life sciences, LZU did in-depth research on the mechanism of transcriptional expression and control of IL6.
In response to IFNβ, the IL6 gene is activated, modestly at early times by ISGF3 (IRF9 plus tyrosine-phosphorylated STATs 1 and 2), and strongly at late times by U-ISGF3 (IRF9 plus U-STATs 1 and 2, lacking tyrosine phosphorylation). A classical IFN-stimulated response element (ISRE) at −1,513 to −1,526 in the human IL6 promoter is required. Pretreating cells with IFNβ or increasing the expression of U-STAT2 and IRF9 exogenously greatly enhances IL6 expression in response to the classical NF-κB activators IL1, TNF, and LPS. U-STAT2 binds tightly to IRF9, the DNA binding subunit of ISGF3, and also to the p65 subunit of NF-κB. Therefore, as shown by ChIP analyses, U-STAT2 can bridge the ISRE and κB elements in the IL6 promoter. In some cancer cells, the protumorigenic activation of STAT3 will be enhanced by the increased synthesis of IL6 that is facilitated by high expression of U-STAT2 and IRF9.
The research is co-cooperated by Prof. Yang Jinbo’s research group from school of life sciences, LZU and Prof. George R. Stark’s research group from Cleveland Clinic of America, which is one of the world famous medical institutions. Prof. Yang Jinbo’s research group has kept sound cooperation with Cleveland Clinic for many years and they have sent students and teachers for exchange and communication, all of which have achieved a series of excellent results. This is the third time that Prof. Yang’s team published paper on PNAS since 2011 and 2013. The paper, with its first author as Dr. Nan Jing from school of life sciences, and the corresponding authors as Prof. Yang Jinbo and Prof. George R. Stark, is one of Dr. Nan Jing’s research achievements when he was a visiting scholar in Dr. George R. Stark’s research group. The project is subsidized by Natural Science Foundation of China.
(Translated by Li Xingyi; proofread by Zhang Yina)
