RESUMO
Recent findings provide evidence for a functional interplay between DNA replication and the seemingly distinct areas of cancer, development and pluripotency. Protein complexes participating in DNA replication origin licensing are now known to have roles in development, while their deregulation can lead to cancer. Moreover, transcription factors implicated in the maintenance of or reversal to the pluripotent state have links to the pre-replicative machinery. Several studies have shown that overexpression of these factors is associated to cancer.
Assuntos
Replicação do DNA , Neoplasias/genética , Animais , Diferenciação Celular , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/patologia , Células-Tronco Neoplásicas/fisiologia , Células-Tronco Pluripotentes/fisiologiaRESUMO
NF-kappaB is implicated in lymphocyte development, maturation, proliferation and survival. This inducible transcription factor is widely expressed by virtually all cell types. In mammals, the genes rela, relb, crel, nfkappaΒ1, and nfkappaB encode the five NF-kB protein family members RelA (p65), RelB, c-Rel, p50, and p52, respectively, which form homo- and heterodimeric DNA-binding complexes capable of regulating target gene transcription of specific biological responses differentially. NF-kappaB regulates the expression of a wide variety of genes that play critical roles in innate and adaptive immune responses, is strongly linked to the inhibition of apoptosis, and contributes to tumor growth, metastasis, and chemoresistance. Parasites have targeted several parts of the NF-kappaB pathway, allowing them to interfere with the transcription of immune response genes. The biology of different parasites is critical in influencing the patterns and kinetics of NF-kappaB activity and thereby the development of subsequent immune responses.
Assuntos
Interações Hospedeiro-Parasita/imunologia , NF-kappa B/imunologia , Doenças Parasitárias/imunologia , Imunidade Adaptativa/genética , Animais , Interações Hospedeiro-Parasita/genética , Humanos , Imunidade Inata/genética , Modelos Imunológicos , NF-kappa B/genética , Doenças Parasitárias/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologiaRESUMO
Host resistance against pathogens depends on a complex interplay of innate and adaptive immune mechanisms. Acting as an early line of defence, the immune system includes activation of neutrophils, tissue macrophages, monocytes, dendritic cells, eosinophils and natural killer (NK) cells. NK cells are lymphoid cells that can be activated without previous stimulation and are therefore like macrophages in the first line of defence against tumor cells and a diverse range of pathogens. NK cells mediate significant activity and produce high levels of proinflammatory cytokines in response to infection. Their cytotoxicity production is induced principally by monocyte-, macrophage- and dendritic cell-derived cytokines, but their activation is also believed to be cytokine-mediated. Recognition of infection by NK cells is accomplished by numerous activating and inhibitory receptors on the NK cells' surface that selectively trigger the cytolytic activity in a major histocompability complex-independent manner. NK cells have trypanocidal activity of fibroblast cells and mediate direct destruction of extracellular epimastigote and trypomastigote forms of T. cruzi and T. lewisi in vitro; moreover, they kill plasmodia-infected erythrocytes directly through cell-cell interaction. This review provides a more detailed analysis of how NK cells recognize and respond to parasites and how they mediate cytotoxicity against tumor cells. Also the unique role of NK cells in innate immunity to infection and the relationship between parasites and carcinogenesis are discussed.