Abstract:

Lipopolysaccharide(LPS) has an important function in bacteria-invading cells. Toll-like receptor(TLR) 2 can recognize LPS by forming a heterodimer with TLR1 or TLR6, which then activates cellular immune response by the myeloid differentiation factor(MyD88)-dependent pathway. The death domain of MyD88 raises downstream signaling molecules, such as interleukin(IL)-1 and IL-4 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, transforming growth factor β1 that activates nuclear factor(NF)-κB, and P38 mitogen-activated protein kinase and activator protein(AP) 1, which lead to the production of pro-inflammatory cytokines. MyD88-independent pathway reportedlyactivates the transcription factor interferon regulatory factor 3 and AP1, and can induce the generation of interferon 1 by activating NF-κB, tumor necrosis factor receptor-associated factor 3, and interleukin-1 receptor-1. CD14 and MyD2 are required for LPS binding to TLR4. Preventing CD14/MyD2-mediated binding of LPS to TLR4 could block inflammatory response at the outset. TLR2 and TLR4 are crucial in LPS-induced inflammation. Inhibiting the expression of TLR2 and TLR4 will be an effective and direct way to control the inflammation. A better understanding of the regulation of TLR2 and TLR4 signaling pathways will provide further support to their potential therapeutic application to periodontitis, inflammatory bowel disease, cardiovascular disease, and autoimmune diseases.

Key words: Toll-like receptor, signal pathway, pathway inhibition, inflammatory treatment