Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways
- Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways
- 박현호; 베드리칸난
- TOLL-LIKE RECEPTORS; NF-KAPPA-B; INNATE IMMUNE; ADAPTER MOLECULE; IL-1 RECEPTOR; CRYSTAL-STRUCTURE; DROSOPHILA TOLL; DIFFERENTIAL INVOLVEMENT; INFLAMMATORY DISEASES; BACTERIAL-INFECTIONS
- Issue Date
- APOPTOSIS, v.20, no.2, pp.196 - 209
- Innate immunity, which is the first line of host defense against invading microbial pathogens in multicellular organisms, occurs through germline-encoded pattern-recognition receptors. The Toll-like receptor/Interleukin (IL)-1 receptor (TLR/IL-1R) superfamily comprises proteins that contain the phylogenetically conserved Toll/IL-1 receptor (TIR) domain, which is responsible for the propagation of downstream signaling through recruitment of TIR domain containing cytosolic adaptor proteins such as MyD88, TIRAP/MAL, TRIF, TRAM and SARM. These interactions activate transcription factors that regulate the expression of various proinflammatory cytokines (IL-1, IL-6, IL-8 and TNF-alpha) and chemokines. Activation of the TLR/IL-1R signaling pathway promotes the onset of inflammatory diseases, autoimmune diseases and cancer; therefore, this pathway can be used for the development of therapeutic strategies against these types of pathogenesis. In this review paper, we illustrate the role of the TIR-TIR domain interaction with the TLR/IL-1R signaling pathway in inflammation and apoptosis and recent therapeutic drugs targeted to inhibit the downstream signaling cascade for treatment of inflammatory diseases and cancer.
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