Toll-like receptor 9 and vascular endothelial growth factor levels in human kidneys from lupus nephritis patients

Abstract

In the lupus mouse and systemic lupus erythematosus (SLE) patients, DNA fragments isolated from plasma may mimic microbial DNA and trigger Toll-like receptor 9 (TLR9) signaling with formation of autoantibodies against DNA fragments and nucleosomes. Vascular endothelial growth factor (VEGF) is a tightly regulated angiogenic cytokine in the kidney. The present study investigated glomerular and tubular expression of both TLR9 and VEGF in biopsies from human subjects with lupus nephritis (LN) and normal controls. Kidney biopsies in LN (n=8) and normal controls (n=10) were evaluated for expression of TLR9 and VEGF. The degree of kidney damage was analyzed according to the International Society of Nephrology / Renal Pathology Society classification. Immunohistochemistry was performed, and slides were incubated with antibodies against VEGF and TLR9 monoclonal antibody, stained with hematoxylin and eosin, mounted and microscopically scored at ×10 and ×20. We observed intense staining of glomeruli and tubules for TLR9 up to 3+ from patients with LN. Samples from LN subjects showed 3+ staining of glomeruli but only up to 2+ in tubules for VEGF. There was less significant staining for TLR9 and none for VEGF in controls. There was no correlation observed between LN class severity and intensity of staining for VEGF or TLR9. This is the first study that investigated combined expression of TLR9 and VEGF, which could be an important tool for understanding the role of TLR9 and VEGF in LN, with insights into the early detection and targeted treatment of this disease.