Effect of lipid-bound apolipoprotein A-I cysteine mutant on ATF3 in RAW264.7 cells

Activating transcription factor 3 (ATF3) is a TLR-induced repressor that plays an important role in the inhibition of specific inflammatory signals. We previously constructed recombinant high density lipoproteins (rHDL) (including rHDL(WT), rHDL(M), rHDL(228) and rHDL(74)) and found that rHDL(74) had a strong anti-inflammatory ability. In the present study, we investigate the roles of recombinant apolipoprotein A-I (ApoA-I) (rHDL(WT)) and its cysteine mutant HDLs (rHDL(M), rHDL(228) and rHDL(74)) on ATF3 function in RAW264.7 cells stimulated by lipopolysaccharide. Our results showed that compared with the LPS group, rHDL(74) can decrease the level of TNF-α and IL-6, whereas rHDL(228) increases their expression levels. RT-PCR and Western blotting results showed that compared with the LPS group, rHDL(74), rHDL(WT) and rHDL(M) can markedly increase the expression level of ATF3, whereas the level of ATF3 decreases in the rHDL(228) group. In summary, the different anti-inflammatory mechanisms of the ApoA-I cysteine mutants might be associated with the regulation of ATF3 level.