Chloroquine Differentially Modulates Inflammatory Cytokine Expression in RAW 264.7 Cells in Response to Inactivated Staphylococcus aureus

The anti-inflammatory property of chloroquine (CQ) has long been recognized. This study aimed to investigate the effect of CQ on proinflammatory cytokine expression in RAW 264.7 macrophages stimulated with heat-inactivated Staphylococcus aureus cells (SAC). The results showed that CQ treatment reduced the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and CC chemokine ligand 2 (CCL2) in culture medium but increased intracellular protein expression of TNF-alpha and CCL2 in SAC-activated cells. However, CQ showed differential effects on their messenger RNA (mRNA) levels: it reduced IL-6 mRNA expression, increased CCL2 mRNA levels, but had no effect on TNF-alpha mRNA. The SAC-activated inflammatory signaling pathways were slightly or minimally affected by CQ treatment. Additionally, CQ increased the accumulation of pro-TNF-alpha proteins within cells, suggesting an inhibition of pro-TNF-alpha processing and secretion. Collectively, CQ differentially modulated proinflammatory cytokine expression in Gram-positive bacterium-activated macrophages at multiple regulatory layers in the course of their biosynthesis.