tor proteins, leading to NF-kB release and translocation to the nucleus, eventually activating the transcription of target genes involved in inflammation. Whole genome microarrays on parasitized Drosophila melanogaster by Leptopilina species revealed gene activation of Toll/NF-kB and JAK/STAT pathway components, involved in regulating immune responses toward microbes and macroparasites. The up-regulation of genes involved in these particular immune pathways suggests these hosts are better protected against microorganisms at parasitoid oviposition. In endoparasitoid venoms, the PDVs encode proteins with ankyrin repeats that are also found in Cactus, the inhibitor protein of NF-kB signaling in Drosophila, and in mammalian IkB family members. These viral ankyrin repeats however, lack the amino acid sequences necessary for their degradation/turnover. Therefore, they act as antagonists of NF-kB nuclear translocation, hence supporting parasite success. During the last decade, several PDVs in endoparasitoids have been found to express IkB-related vankyrin genes that suppress NF-kB activity during immune responses in parasitized hosts. In mammalian organisms, the nuclear factor kappa B transcription factors regulate important physiological processes, including inflammation and immune responses. Maintenance of appropriate levels of NF-kB activity is a critical factor in immune system development and normal cell proliferation. Aberrant activation of the NF-kB pathway is involved in the pathogenesis of a LY341495 manufacturer number of human diseases including those related to inflammation, enhanced cellular proliferation, viral infection and genetic diseases. Asthma for instance is a chronic inflammation of the bronchial tubes, of which the activation of NF-kB is stimulated by agents such as allergens, ozone and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19656604 viral infections. NF-kB also participates in many aspects of oncogenesis, since it can suppress apoptosis and induce expression of proto-oncogenes. The constitutive NF-kB activity has been observed in a number of human cancers and the inhibition of NF-kB abrogates tumor cell proliferation. Regulation and control of NF-kB activation can be a powerful therapeutic strategy for inhibiting tumor growth and viral infections and for reducing the tissue damage that follows the release of inflammatory mediators. Various stimuli give rise to the phosphorylation and degradation of the inhibitor of NF-kB via the IkB kinase complex, leading to NF-kB release and translocation to the nucleus, eventually activating the transcription of target genes involved in inflammation. On the other hand, activation of mitogenactivated protein kinases, including extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinase, is another major signal transduction pathway involved in inflammation and is closely linked to the activation of the NF-kB pathway. It is clear that deregulation of the transcription factor NF-kB can mediate several inflammatory diseases. Therefore several proteins tightly control its activation. Among these proteins are the NF-kB inhibitory proteins, IkBa and A20, the expression of which leads to a negativefeedback response that terminates activation of NF-kB. Moreover, the NF-kB inflammatory response is also modulated by endogenous glucocorticoids that are released following a challenge with various cytokines, with the aim to restore homeostasis. These GCs are steroid hormones that can diffuse freely across the plasma membrane and bind to their intracell
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