title: Immunoregulatory effects of sinomenine on the T-bet/GATA-3 ratio and Th1/Th2 cytokine balance in the treatment of mesangial proliferative nephritis.
abstract: Sinomenine has been used to treat autoimmune diseases for centuries. However, the mechanism underlying its therapeutic effects remains unknown. Increasing recognition of the importance of the Th1/Th2 imbalance in nephritis has raised the questions of whether there is a Th1/Th2 imbalance in patients with mesangial proliferative nephritis (MsPGN) and whether sinomenine can modulate the Th1/Th2 imbalance. In this study, 25 MsPGN patients were treated with sinomenine and followed for 3 months. The expression of T-bet and GATA-3 mRNA in peripheral blood mononuclear cells (PBMCs) and the serum levels of interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-10 were studied at month 0, month 1, and month 3. The intra-renal expression of T-bet and GATA-3 was studied via immunohistochemistry. Results reveal that PBMCs from MsPGN patients expressed high levels of T-bet mRNA and low levels of GATA-3 mRNA, and the T-bet/GATA-3 ratio in MsPGN patients was significantly higher than that in healthy donors. Meanwhile, MsPGN patients were found to have simultaneously elevated IFN-gamma values and decreased IL-10 values. Immunohistochemistry revealed increased T-bet and decreased GATA-3 expression in renal tissues from MsPGN patients. Moreover, sinomenine was found to cause a decrease in T-bet mRNA expression, resulting in a drop in the T-bet/GATA-3 ratio. Sinomenine was also found to elicit a decrease in the serum levels of IFN-gamma. These results suggest that a shift toward the Th1 pathway of Th cell activation occurs in MsPGN patients, and that sinomenine has the potential to counter this shift in the Th1/Th2 balance and thereby produce therapeutic effects.
authors.affiliation: Department of Nephrology, Xinqiao Hospital, PLA, The Third Military Medical University, Chongqing 400037, PR China. chengyue20022@hotmail.com
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Weiping
authors.initials: W
authors.lastname: Hou
authors.forename: Daihong
authors.initials: D
authors.lastname: Wang
authors.forename: Furong
authors.initials: F
authors.lastname: Li
authors.forename: Yaoquan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fahuan
authors.initials: F
authors.lastname: Yuan