Toll/IL-1 receptor

Su, X., Li, S., Meng, M., Qian, W., Xie, W., Chen, D., Zhai, Z. et al., TNF receptor-associated factor-1 (TRAF1) negatively regulates Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-mediated signaling. Eur J Immunol 36 (2006) 199-206. 

O Neill, L. A., Fitzgerald, K. A., and Bowie, A. G. (2003). The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 24, 286-290. 

It is now believed that the developmental function of the Tolls in flies (so-called to distinguish them from the mammalian TLRs) is something of an evolutionary digression. This belief is predicated largely on the fact that in still more divergent species (notably plants), the conserved TIR domain (Toll/IL-1 receptor/resistance), which comprises most of the cytoplasmic domain of all of the Toll-like receptors,... 

Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, Akira S (2003) Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol, 171(8) 4304-4310. 

SULLIVAN C, POSTLETHWAIT JH, LAGE CR, MILLARD PI, KIM CH (2007), EvidCUCe foi evolving Toll-IL-1 receptor-containing adaptor molecule function in vertebrates , / Immunol, 178,4517-27. 

IL-1 receptor associated kinase family-A with Toll-like receptor signalling. There are four members in this group to date IRAK-1,2,4 and M. They can phosphor-ylate among themselves, as well with other proteins involved in signalling such as TRAF-6. 

Koziczak-Holbro M, Joyce C, Gluk A, Kinzel B, et al. 2007. IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor-7 mediated signaling and gene expression. J Biol Chem. 282 13552-13560. 

O Neill LA. 2002. Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily. Curr Top Microbiol Immunol. 270 47-61. 

Figure 8.3. Various neurotoxins induce the expression of inducible nitric oxide synthase (iNOS) via the activation of NF-kB. Nitric oxide produced from iNOS then induces the activation of guanylate cyclase (GUCY) that catalyzes the production of cGMP. Inhibition of phosphodiesterase may also increase the level of cGMP. Cyclic GMP utilizes protein kinase G (PKG) to increase the expression of GFAP. IL-IR, IL-1 receptor TLR4, toll-like receptor4 GPCR, G protein-coupled receptor TLR3, toll-like receptor 3.

Bellocchio S, Montagnoli C, Bozza S et al. The contribution of the toll-likc/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J Immunol 2004 172 3059-3069. 

Tumor necrosis factor receptor associated factors are a group of at least 6 proteins (TRAF 1-6), which are major signal transducers for the TNF receptor superfamily and the the interlukin-1 receptor/toll-like receptor (IL-1R/ TLR) superfamily. TRAF proteins are characterized by the presence of the TRAF domain at the the C-terminus,... 

In monocytes stimulated with Toll-like receptor-triggering bacterial products, histamine inhibits the production of proinflammatory IL-1-like activity, TNF-a, IL-12 and IL-18, but enhances IL-10 secretion, through HR2 stimulation [26, 69]. Histamine also downregulates CD 14 expression via Hj receptors on human monocytes [70]. The inhibitory effect of histamine via Hj receptor appears through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS [71]. 

Endotoxicity results from the interaction of a bacterial cell envelope component (e.g., LPS or PG with a cell surface receptor constituting part of the nonspecific immune system, (i.e., a toll-like receptor on white blood cells). This results in the production of cytokines [e.g., interleukin 1 (IL-1) or tumor necrosis factor (TNF)] as part of an intracellular enzyme cascade which can cause severe tissue injury. Bioassays or immunoassays can be used to detect such reactions respectively. As noted above the most widely used bioassay is the LAL assay. A lysate of amoebo-cytes of the horseshoe crab (Limulus) contains an enzymatic clotting cascade which is activated by extremely low levels of LPS (nanogram levels or lower). There are variants of this assay that can detect PG, but they are not as widely used. As noted above, other bioassays employ cultured cell lines that respond to LPS or PG, respectively. Unfortunately bioassays are highly amenable to false positives (from the presence of cross-reactive substances) or false negatives from inhibition (by contaminants present in the sample) [10]. A detailed discussion of these assays is beyond the scope of this chapter and has been reviewed elsewhere [1]. 

Rao, N., Nguyen, S., Ngo, K., Fung-Leung, W.P. A novel splice variant of interleukin-1 receptor (IL-lR)-associated kinase 1 plays a negative regulatory role in Toll/IL-lR-induced inflammatory signaling. Mol Cell Biol 25 (2005) 6521-6532. 

Serine proteases, released from immune cell granules, process cytokines and growth factors that control multiple cellular process [56], Proteinase 3, cathepsin G, and elastase all cleave membrane-bound TNF-o, IL-1, and IL-18, and activate epidermal growth factor receptor (EGFR) and toll-like receptor-4 (TLR-4). These actions inhibit growth and lead to apoptosis with transcriptional nuclear factor kB (NF-kB) inactivation. Bik suppresses release of TNF-o, IL-1, and IL-18 and prevents EGFR and TLR-4 activation. Activation of NF-kB is a mediator of cell proliferation, whereas inhibition of NF-/. B leads to apoptosis [82]. Overall, Bik inhibition of immune cell serine proteases increases cell proliferation and stability. 

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