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Gene-environment interactions influence cytokine biology in immunotoxicity and disease: genomic, genetic, and epigenetic perspectives.
Toxicologist 2010 Mar; 114(1):2
Cytokines are key signaling and effector molecules that regulate many aspects of host response to exogenous stressors. To date, animal and human studies have identified individual and interacting effects of cytokines at different stages in the pathogenesis of chronic inflammatory and immune-mediated diseases. Animal studies utilizing gene knock-out and transgenic animals and expression microarrays have identified disease-related cytokine networks. Human studies using various genome screening efforts have also uncovered potential candidate genes for disease development and progression. Cytokine genes and their receptors are highly polymorphic and variations in these genes have been associated with the course of and susceptibility to a variety of diseases including infectious, inflammatory, and autoimmune. In addition, epigenetic changes including altered DNA methylation and histone acetylation can control cytokine gene expression by changing the transcription-permissive nature of chromatin structure. Environmental factors are known to modify the direction and magnitude of disease risk in an environment-specific manner. In this respect, genetic association studies have identified interactions between cytokine gene variations and environmental/occupational exposures as shown in the case of silicosis and asthma. In addition, recent studies demonstrated that environmental exposures might alter methylation states of key cytokines genes supporting an epigenetic gene-environment interaction. This course will address aspects of the current state of knowledge with respect to genomic, genetic, and epigenetic approaches in the investigation of cytokine genes associated with occupational and environmental-related diseases.
Biological-effects; Cell-biology; Chemical-hypersensitivity; Environmental-exposure; Epidemiology; Exposure-assessment; Exposure-levels; Exposure-methods; Genetic-factors; Laboratory-testing; Occupational-exposure; Particle-aerodynamics; Particulates; Respiratory-hypersensitivity; Toxic-effects
Issue of Publication
Healthcare and Social Assistance; Services
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah