Therefore, structure and conformation of ER-α/pER-α protein molecule and the nature of its interactions with different TLR2 ligands and estrogen have profound importance in female gender-predominant autoimmune lupus. Our observations also suggested that the ER-α inhibitor MPP reduced pER-α (Serine 118) at 66 kDa in the nuclear extracts of MRL/lpr kidney mesangial cells. The band intensities at 100 kDa and 45 kDa were altered with increasing MPP doses. Additionally, immunoprecipitation of ER-α and western blot analysis

of pER-α (Serine 118) suggested that ER-α/pER-α was a major band at 66 kDa. Similar observations were also found for pER-α (Serine 104/106) in mesangial cells. Furthermore, we found that exogenous estrogen inhibited TLR2-mediated MCP1 production, although estrogen alone barely has any effect on the production of the inflammatory chemokine MCP1 in mesangial cells. Thus, we suggest a dual responsive role for ER-α toward BMS-354825 mw TLR2 signaling and estrogen-mediated signaling in mesangial cells. Our observations, along with findings from other laboratories, Crizotinib suggested that attenuation of mesangial cell activation is an important step for the management of autoimmune nephritis. Autoimmune SLE is found in female patients during childbearing years, when estrogen plays a vital physiological

role. However, our observations and also the findings from other laboratories indicated the beneficial importance of estrogen in the prevention of mesangial cell activation. Therefore, endogenously synthesized estrogen in female SLE patients is not sufficient to combat the severity of disease

progression. There is a possibility that autoantibodies, complement and immune complexes activate TLR2-mediated inflammatory signaling, which suppresses estrogen-mediated anti-inflammatory responses in the kidneys. Thus, the inhibition of TLR2-mediated inflammatory signals and a decrease in MCP1 expression in kidney mesangial cells are important for the attenuation of inflammation in several ways. The attenuation of estrogen-independent ER-α activation signaling as well as the selective use of estrogenic compounds and estrogen-like ER-α modifiers (SERMs) are found possible targets for therapy in kidney inflammation. Favoring Bcl-w these possibilities, we found that ER-α/pER-α (Serine 118) is an intermediate common regulator for both estrogen-mediated anti-inflammatory pathways and TLR2-mediated inflammation-induced NF-kB activation in mesangial cells in kidney glomeruli. The anti-inflammatory role of estrogen has been demonstrated in murine models of renal disease. Estradiol was found to reverse TGF-β mediated renal injury in Alb/TGF-beta1 transgenic mice and p53 knockout mice [35,36]. On the other hand, Potier et al. [37] indicated that there were limitations of estrogen in the treatment of genetically susceptible glomerulosclerosis in mice.