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Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways

  • The Domains of Apoptosis and Inflammation
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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.

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Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) of the Ministry of Education, Science and Technology (2012R1A2A2A01010870).

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The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. School of Biotechnology and Graduate School of Biochemistry, and Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, 712 749, South Korea

    Kannan Badri Narayanan & Hyun Ho Park

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  1. Kannan Badri Narayanan
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  2. Hyun Ho Park
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Correspondence to Kannan Badri Narayanan or Hyun Ho Park.

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Narayanan, K.B., Park, H.H. Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways. Apoptosis 20, 196–209 (2015). https://doi.org/10.1007/s10495-014-1073-1

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  • DOI: https://doi.org/10.1007/s10495-014-1073-1

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