Clark Lantz
Work Summary
We are interested in the effects of early life exposures to environmental toxicants on lung growth and development. We determine if the early life exposures leads to adult disease.
We are interested in the effects of early life exposures to environmental toxicants on lung growth and development. We determine if the early life exposures leads to adult disease.
The NF-E2 p45-related factor 2 (Nrf2) signaling pathway regulates the cellular antioxidant response and activation of Nrf2 has recently been shown to limit tissue damage from exposure to environmental toxicants, including As(III). In an attempt to identify improved molecular agents for systemic protection against environmental insults, we have focused on the identification of novel medicinal plant-derived Nrf2 activators.
The effects of JP-8 on pro-inflammatory cytokine interleukin (IL)-1alpha,beta and nitric oxide (NO) secretion as well as the role of substance P (SP) in these processes were examined in cultured alveolar macrophages (AM), type II epithelial cells (AIIE), and AM/AIIE co-cultures. Exposure of AM to JP-8 for 24 hr exhibited release of IL-1alpha,beta, whereas exposure to AIIE showed a concentration-dependent NO overproduction. Data indicate that there are cell-dependent inflammatory mechanisms responsible for the actual level of JP-8 exposure in alveoli. However, treatment with substance P significantly attenuated JP-8 induced the IL-1alpha,beta secretion. This finding was confirmed by using [Sar(9) Met (O(2))(11)] SP (10(- 10) M), an agonist of substance P, suggesting that substance P may have signal pathway(s) to AM in the inflammatory response mediated by IL-1. Moreover, AM/AIIE co-culture obviously reduced NO overproduction observed in AIIE alone, suggesting that there may be cell interactions or communications between AM and AIIE in response to the JP-8 exposure.