Sirtuin 1 inhibits lipopolysaccharide-induced inflammation in chronic myelogenous leukemia k562 cells through interacting with the Toll-like receptor 4-nuclear factor kappa B-reactive oxygen species signaling axis.

Background: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative neoplasm resulting from BCR-ABL-transformed hematopoietic stem cells. Previous research has implicated multifunctional proinflammatory cytokines in CML development. It has been reported that Sirtuin 1 (SIRT1) as well as ADP-ribosyltransferase and deacetylase may influence CML cell viability and inflammation. Methods: This study was directed toward exploring the SIRT1-involved in the mechanism of lipopolysaccharide (LPS)-triggered inflammation in CML k562 cells. Results: In our study, the LPS-induced inflammation in k562 cells was reflected by increases in levels of diverse inflammatory cytokines, including interleukin (IL)-10, IL-1beta, IL-6, interferon-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta. LPS also decreased SIRT1 expression and nuclear location in k562 cells. Furthermore, SIRT1 overexpression inhibited the release of the above mentioned cytokines in LPS-treated cells. We also determined that LPS stimulation could activate Toll-like receptor 4 (TLR4), the nuclear factor kappa B (NFkappaB) subunit, and p65 and produce reactive oxygen species (ROS) in k562 cells. Nevertheless, SIRT1 overexpression decreased TLR4 expression, thereby repressing the phosphorylation of the NFkappaB subunit and p65 and decreasing ROS production. Conclusions: These findings suggest that SIRT1 is a latent therapeutic target for mitigating LPS-induced inflammation via the TLR4-NFkappaB-ROS signaling axis.