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, rHDL₂₂₈ and rHDL₇₄) and found that rHDL₇₄ 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, rHDL₂₂₈ and rHDL₇₄) on ATF3 function in RAW264.7 cells stimulated by lipopolysaccharide. Our results showed that compared with the LPS group, rHDL₇₄ can decrease the level of TNF-α and IL-6, whereas rHDL₂₂₈ increases their expression levels. RT-PCR and Western blotting results showed that compared with the LPS group, rHDL₇₄, rHDL_WT and rHDL_M can markedly increase the expression level of ATF3, whereas the level of ATF3 decreases in the rHDL₂₂₈ group. In summary, the different anti-inflammatory mechanisms of the ApoA-I cysteine mutants might be associated with the regulation of ATF3 level.