Though the mechanism of glomerular inflammation is not clear, it is known that auto-antibody production, complement cascade activation and formation of immune complexes have an impact on inflammation and the progression of disease in susceptible hosts [32]. The importance of extracellular innate immune receptor TLR2 in glomerulonephritis depends largely on the nature of check details its interaction with endogenously derived ligands and environmental factors via a mechanism that is not yet clear. Our observations suggested that, at an early stage of life, TLR2 agonists play an important role in mesangial cell activation and inflammation. We found that mesangial cells from 4 to 6 week old lupus-susceptible MRL/lpr

mice and from lupus-unrelated C57BL/6 mice respond similarly to TLR2 agonists to produce MCP1 in vitro. The overall immune responses in lupus-susceptible MRL/lpr mice start at 15–16 weeks and attain a peak value at 20–22 weeks of age. TLR2 agonist(s) this website exacerbate the immune responses, including B cell activation, in these 20–22 week old mice ( Dasgupta S., Molano I. Specific antigenic recognition shifts a balance from tolerance to effector immune responses in lupus cerebritis.

J. Immunol. (Abstract) 2012 188: 173.34). . Thus, antigen-specific activation of TLR2 plays an important role in inflammatory immune responses in mesangial cells. The infiltration of neutrophils, CD11b and CD3ɛ can be correlated with increased MCP1 production and the increase in TLR2 expression in mesangial cells (Dasgupta et al., unpublished observations). These infiltrating immune cells take part in localized inflammatory responses and cause tissue damage during progression of disease. Our observations in primary mesangial cells suggested that estrogen receptor-alpha (ER-α) takes part in TLR2 agonist-mediated MCP1 production. We found that

TLR2 ligands and estrogen, either alone or in combination, induced phosphorylation of ER-α at Serine 118 and Serine 104/106 in mesangial cells. The phosphorylation of estrogen receptor-alpha at Serine 118 and Serine104/106 residues causes activation of ER-α [30,31,33]. However, the consequences for such phosphorylation and thus an altered protein conformation of pER-α are still not known in a physiological context and in the onset of female-predominant Thymidine kinase autoimmune disease. The phosphorylation–dephosphorylation process plays a key role not only in receptor activation but also in the alteration of its protein structure and conformation, which is an essential part of the receptor–ligand interaction. Although TLR2 agonists and estrogen both have the ability to phosphorylate ER-α at Serine 118 and Serine 104/106, our observations did not demonstrate any remarkable synergistic effect for the agonists and estrogen on ER-α phosphorylation in mesangial cells. The findings indicated a saturation level of serine amino acid phosphorylation at the 118 and 104/106 sites of the ER-α protein molecule. Recently, Colasanti et al.