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Nrf-2 Inducers Ameliorate Hyperoxia-Compromised Macrophage Functions
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A6372 - Nrf-2 Inducers Ameliorate Hyperoxia-Compromised Macrophage Functions
Author Block: K. Dial, W. Wu, M. Wang, J. Wu, L. Mantell; St. John's University, Jamaica, NY, United States.
Prolonged exposure to hyperoxia (>95% O2) has been shown to contribute to the accumulation of HMGB1 in the airways of patients receiving oxygen therapy. Excessive production of intracellular reactive oxygen species (ROS) during prolonged hyperoxia exposure leads to the oxidation of actin, compromising the ability of alveolar macrophages to form a phagocytic cup around invading pathogens. Compromise of innate immunity by hyperoxia predisposes patients receiving ventilation to developing ventilator associated pneumonia (VAP). Nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) is a transcription factor that regulates the expression of endogenous antioxidant proteins. The present study investigates whether sulforaphane (SUL) and resveratrol (RES), Nrf-2 inducers, can ameliorate hyperoxia-compromised macrophage functions. RAW 264.7 cells, a murine macrophage-like cell line, and bone marrow-derived macrophages (BMDM) were exposed to hyperoxia for 24 hours in the presence or absence of different concentrations of SUL or RES. SUL treatment ameliorated the increase of intracellular levels of reactive oxygen species (ROS) as well as hyperoxia-induced compromised phagocytic function. In addition, SUL was found to rescue rHMGB1 compromised macrophage phagocytosis. Furthermore, both SUL and RES were found to inhibit HMGB1 release, activate Nrf-2, and increase levels of the endogenous antioxidant compound, HO-1. This increase in macrophage phagocytic function in the presence of Nrf-2 inducing compounds suggests that enhanced antioxidant capacity through the activation of the Nrf-2 pathway can improve innate immunity, providing a therapeutic approach to the treatment of VAP.
Author Block: K. Dial, W. Wu, M. Wang, J. Wu, L. Mantell; St. John's University, Jamaica, NY, United States.
Prolonged exposure to hyperoxia (>95% O2) has been shown to contribute to the accumulation of HMGB1 in the airways of patients receiving oxygen therapy. Excessive production of intracellular reactive oxygen species (ROS) during prolonged hyperoxia exposure leads to the oxidation of actin, compromising the ability of alveolar macrophages to form a phagocytic cup around invading pathogens. Compromise of innate immunity by hyperoxia predisposes patients receiving ventilation to developing ventilator associated pneumonia (VAP). Nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) is a transcription factor that regulates the expression of endogenous antioxidant proteins. The present study investigates whether sulforaphane (SUL) and resveratrol (RES), Nrf-2 inducers, can ameliorate hyperoxia-compromised macrophage functions. RAW 264.7 cells, a murine macrophage-like cell line, and bone marrow-derived macrophages (BMDM) were exposed to hyperoxia for 24 hours in the presence or absence of different concentrations of SUL or RES. SUL treatment ameliorated the increase of intracellular levels of reactive oxygen species (ROS) as well as hyperoxia-induced compromised phagocytic function. In addition, SUL was found to rescue rHMGB1 compromised macrophage phagocytosis. Furthermore, both SUL and RES were found to inhibit HMGB1 release, activate Nrf-2, and increase levels of the endogenous antioxidant compound, HO-1. This increase in macrophage phagocytic function in the presence of Nrf-2 inducing compounds suggests that enhanced antioxidant capacity through the activation of the Nrf-2 pathway can improve innate immunity, providing a therapeutic approach to the treatment of VAP.
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