Primers on Molecular Pathways: Lipopolysaccharide Signaling - Potential Role in Pancreatitis and Pancreatic Cancer

The innate immune system recognizes the presence of bacterial pathogens through the expression of a family of membrane receptors known as Toll-like receptors (TLRs). Lipopolysaccharide (LPS) is specifically recognized by TLR4. Recognition of microbial components by TLRs initiates signal transduction pathways, which triggers expression of genes. These gene products control innate immune responses and further instruct development of antigen-specific acquired immunity. TLR signaling pathways are finely regulated by TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF and TRAM. LPS can act not only on immune cells but also on some types of epithelial cells including cancer cells and promote its transformed phenotype. Specifically, LPS can activate NF-κB signaling in pancreatic cancer cells, thus connecting inflammation with cancer progression. The TLR4 signaling pathway may offer a useful therapeutic target for patients with pancreatitis or pancreatic cancer associated with inflammation.