Interleukin complex

Vigers, G.P.A., et al. Crystal structure of the type-1 interleukin-1 receptor complexed with interleukin-ip. Nature 386 190-194, 1997. 

Inflammatory caspases (caspase-1, -4, -5,-11 and -12) constitute a subgroup of the caspase family. Caspase-1 is the best characterized member and is responsible for the proteolytic maturation and release of the pro-inflammatory cytokines pro-interleukin (IL)-1 (3 and pro-IL-18. Caspase-1 gets activated in inflammasome complexes upon cellular stress, cellular damage and infection. 

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

Figure 38-7. Activation of elF-4E by insulin and formation of the cap binding elF-4F complex. The 4F-cap mRNA complex is depicted as in Figure 38-6. The 4F complex consists of elF-4E (4E), elF-4A, and elF-4G. 4E is inactive when bound by one ofa family of binding proteins (4E-BPs). Insulin and mitogenic factors (eg, IGF-1, PDGF, interleukin-2, and angiotensin II) activate a serine protein kinase in the mTOR pathway, and this results in the phosphorylation of 4E-BP. Phosphorylated 4E-BP dissociates from 4E, and the latter is then able to form the 4F complex and bind to the mRNA cap. These growth peptides also phosphorylate 4E itself by activating a component of the MAP kinase pathway. Phosphorylated 4E binds much more avidly to the cap than does nonphosphorylated 4E.

Clubb RT, Omichinski JG, Clore GM, Gronenbom AM. Mapping the binding surface of interleukin-8 complexes with an N-terminal fragment of the type 1 human interleukin-8 receptor. FEBS Lett 1994 338 93-7. 

Skelton NJ, Quan C, Reilly D, Lowman H. Structure of a CXC chemokine-receptor fragment in complex with interleukin-8. Structure 1999 7 157-68. 

Wada T, Tomosugi N, Naito T, et al. Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis. J Exp Med 1994 180 1135-1140. 

Kumar, V., Bhardwaj, V., Soares, L., Alexander, J., Sette, A. and Sercaz, E. (1995) Major histocompatibility complex binding affinity of an antigenic determinant is crucial for the differential secretion of interleukin 4/5 or interferon-y by T cells. Proceedings of the National Academy of Sciences USA 92, 9510-9514. 

Tsudo, M., Kozak, R.W., Goldman, C.K., and Waldmann, T.A. (1987) Demonstration of a non-Tac peptide that binds interleukin 2 A potential participant in a multichain interleukin 2 receptor complex. Proc. Natl. Acad. Sci. USA 83, 9694-9698. 

The sum total of biological responses induced by the interleukins is large, varied and exceedingly complex. These cytokines regulate a variety of physiological and pathological conditions, including ... 

Martin, M. and Falk, W. 1997. The interleukin-1 receptor complex and interleukin-1 signal transduction. European Cytokine Network 8(1), 5-17. 

FIGURE 27-3 Neurotrophic cytokines and their receptors. Neurotrophic cytokines are related to IL6 and bind to cell surface receptor complexes that share a common structural organization. The four ligands interchangeably employ two distinct receptor subunits, leukemia inhibitory factor receptor 3 (LIF-Rpt) andgpl30, and some employ a ligand-specific a subunit. CNTF-R, ciliary neurotrophic factor CT-fR.cardiotrophin 1 receptor IL6-R, interleukin-6 receptor. 

Local inflammatory changes occur in the joint capsule and synovium. The synovium becomes infiltrated with T cells, and immune complexes appear. Crystals or cartilage shards in synovial fluid may contribute to inflammation. There are also increased levels of interleukin-1, prostaglandin E2, tumor necrosis factor-a, and nitric oxide in synovial fluid. Inflammatory changes result in effusions and synovial thickening. 

Sepsis involves a complex interaction of proinflammatory (e.g., tumor necrosis factor-a [TNF-a] interleukin [IL]-1, IL-6) and antiinflammatory mediators (e.g., IL-1 receptor antagonist, IL-4, and IL-10). IL-8, plateletactivating factor, and a variety of prostaglandins, leukotrienes, and thromboxanes are also important. 

Hora et al. [3.19] described the complexity of protein stabilization by the example of recombinant, human Interleukin-2 (rhIL-2). Formulations with amino acids and mannitol/ sucrose are sensitive to mechanical stress e. g. by pumping. Hydroxypropyl-beta-cyclodextrin (HPcD) provides stability, but increases the sensitivity to oxygen. Polysor-bate 80 forms a mechanically stable product, but results in oxidation. In both cases contamination in the HPcD or traces of H202 in the Polysorbate may have been the starter for the oxidation. Brewster [3.20] reports, that HPcD stabilizes interleukin without forming aggregations and this results in 100 % biopotency. 

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