Manganese superoxide dismutase induced by lipoteichoic acid isolated from Staphylococcus aureus regulates cytokine production in THP-1 cells.

Lipoteichoic acid isolated from Staphylococcus aureus (aLTA) is known to regulate the production of pro-inflammatory cytokines through TLR2-mediated signaling pathways. In our previous study, we found that aLTA significantly increased manganese superoxide dismutase (MnSOD) in the THP-1 human monocyte-like cell line, but the role of MnSOD in the regulation of cytokine production was not elucidated. In the current study, we found that MnSOD was involved in aLTA-mediated cytokine production. The signaling pathways associated with aLTA-mediated MnSOD induction in THP-1 cells included TLR2-MyD88-IRAK2, JNK (c-Jun N-terminal kinases)1/2 and nuclear factor- κB (NF-κB). We also found MnSOD was involved in the regulation of IL-1β and TNF-α, which were induced by early signaling pathways, including JNK1/2, p38, and NF-κB p65. In addition, MnSOD was also involved in the production of IL-6 and CCL2 in aLTA-stimulated THP-1 cells through activation of late signaling pathways such as JAK2-STAT3. Taken together, our data suggest that aLTA-mediated MnSOD production involved in the regulation of cytokine production and it may be the cause of one of the excessive inflammatory reactions caused by S. aureus.