Serum Amyloid A Aggravates Lipopolysaccharide-Induced Injury of BEAS-2B Cells by Activating Toll-Like Receptor 2/Activator Protein-1 Signaling

Abstract

The serum amyloid A (sAA) is a common sensitive indicator for the diagnosis of infectious diseases, and sAA levels are increased in pneumonia. However, the detailed molecular mechanism is unknown. Previous studies have demonstrated the participation of Toll-like receptor (TLR) 2 and its downstream protein activator protein-1 (AP-1) in inflammatory lung injury. This study aimed to investigate the effect of sAA on LPS-induced BEAS-2B cells injury and uncover the possible mechanism. The human bronchial epithelial cell line BEAS-2B was exposed to sAA with or without lipopolysaccharide (LPS) treatment, then cell viability, inflammation and apoptosis were evaluated. The effects of TLR2 knockout on sAA + LPS-treated BEAS-2B cells were also determined. Results revealed that sAA treatment reduced cell viability in a concentration-dependent manner and the effect of 500 nM sAA on cell viability was approximately equivalent to LPS. The levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, monocyte chemotactic protein (MCP)-1 and IL-6 as well as cell apoptosis and expression of proteins related to apoptosis were significantly increased upon sAA or LPS stimulation. The expression of TLR2 and AP-1 was also elevated in cells challenged with sAA or LPS. Besides, sAA and LPS co-treatment further enhanced the actions of LPS. However, the knockdown of TLR2 obviously blunted the effects of LPS and sAA co-treatment on cell viability, inflammation and apoptosis. Taken together, our results revealed that sAA could exert an enhanced effect on LPS-induced BEAS-2B cells injury via promoting TLR2/AP-1 expression.