Abstract: Objective To investigate the role and mechanism of Toll-like receptor 9(TLR-9)in anti-double stranded DNA(anti-dsDNA)antibody production in systemic lupus erythematosus(SLE). Methods Peripheral blood mononuclear cells(PBMC)were isolated from patients with SLE(n=72) and healthy control subjects(n=30)by Ficoll-Hypaque gradient centrifugation, followed by transfection with TLR9 antisense oligonucleotides to abrogate the expression of TLR-9. The PBMC were cultured in the presence with natural calf thymus DNA(nCTDNA)as immunogen, then the anti-dsDNA antibody levels in cell culture supernatants were measured by an enzyme-linked immunosorbent assay(ELISA). Results High levels of anti-dsDNA antibody could be detected in nonsense oligonucleotide (NSON) group, lipofection group, and blank control group. The absorbance value(A value)of each group was 0.79±0.98, 0.76±0.96, 0.81±0.99, respectively. Whereas, the generation of anti-dsDNA antibody was significant inhibited in antisense oligonucleuotide(ASON)group(A value=0.06±0.04, P<0.001).Furthermore, the TLR9 inhibitor chloroquine also significantly reduced the production of anti-dsDNA antibody by nCTDNA-stimulated PBMC from SLE patients(P<0.001). Conclusion These results suggest that TLR9 may play a key role in controlline anti-dsDNA antibody production in SLE.

Key words: Lupus Erythematosus, Systemic, Antibody, antinuclear, TLR9, Chloroquine