Nanoscience is an exciting and rapidly expanding field. Engineered nanomaterials are anticipated for use in many different applications with ever-increasing human exposure. Of these nanomaterials, carbon nanotubes (CNTs) are fullerene-related graphene cylinders that exhibit highly desirable properties, yet also display potentially hazardous traits. Therefore, a careful investigation into potential adverse health effects is a prerequisite for their safe and sustainable development. Pulmonary exposure to CNTs results in oxidative stress, inflammation, granuloma formation, and fibrosis, which may severely impact lung function in affected individuals. Nanomaterials are known to activate the Nlrp3 inflammasome resulting in IL-1?/IL-18 release and acute inflammation in the respiratory tract. The Nlrp3 inflammasome and IL-1?/IL-18 also play critical roles in the regulation of intestinal immune responses. Inflammasome activation, inflammation, and disease pathology following nanomaterial exposure in the respiratory tract have been connected;however, further research is necessary to clarify the impact of CNT exposure on the gastrointestinal (GI) tract. The goal of this proposal is to test the central hypothesis that CNT exposure results in (1) dysregulation of immune responses due to activation of the Nlrp3 inflammasome and aberrant activation of lymphocytes, and (2) altered susceptibility to immune-mediated diseases in the GI tract. We will perform the first characterization of CNTs'toxic potential within the GI tract as a function of dose, time, and route of exposure, define the role of the Nlrp3 inflammasome in this process, and determine the cellular response of the intestinal immune tissues (Aim 1). We will also determine how CNTs affect susceptibility to IBD using the TNBS-induced colitis model (Aim 2). In addition to expanding our knowledge of how CNTs affect the immune system and susceptibility to disease within the GI tract, this research program will advance the field by generating unique and high impact information regarding how exposure to CNTs affects multiple, immune-related endpoints in the context of animal models of common human diseases.
The objective of this proposal is to determine the impact of CNT exposure on the gastrointestinal (GI) tract and the effects of CNT-induced inflammasome activation in acute and chronic models of irritable bowel disease. These studies may lead to a better understanding of immune cell signaling pathways required for immune regulation in the gut.
|Beamer, Celine A; Shepherd, David M (2013) Role of the aryl hydrocarbon receptor (AhR) in lung inflammation. Semin Immunopathol 35:693-704|