title: Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways.
abstract: 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-α) 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.
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry, and Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, 712 749, South Korea, badri.nature@gmail.com.
authors.forename: Kannan Badri
authors.initials: KB
authors.lastname: Narayanan
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D006801:Humans; D007113:Immunity, Innate; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D017472:Receptors, Interleukin-1 / Q000737:chemistry; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors