Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells mustdiscriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Tolllikereceptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, theyhave evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide(LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressedon the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis ofvarious soluble factors and proteins including interleukin-1β, interleukin-8 and TNF-α and apoptosis of THP-1with PGN dose and time dependence. Moreover , in this study we show that PGN induces apoptosis of THP-1cells in a TNF-α-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading totumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxicagents in certain cancers.