Lipoteichoic acid isolated from K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of TNF-α and interleukin (IL)-6. In addition， pLTA increases the survival rate of mice in a septic shock model. In the current study， we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail， pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However， TNF-α production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and TNF-α induced by PGE-2 and LPS in... More
Lipoteichoic acid isolated from K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of TNF-α and interleukin (IL)-6. In addition， pLTA increases the survival rate of mice in a septic shock model. In the current study， we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail， pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However， TNF-α production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and TNF-α induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA， but not by other LTAs isolated from either (aLTA) or (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and TNF-α induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK)， respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231)， which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together， our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.
