FXR is a nuclear receptor that negatively regulates the transcription factor, NFĸB and macrophage inflammatory responses. Herein, we analyzed the role of FXR in lung macrophage activation following exposure of mice to ozone, a pulmonary irritant known to cause macrophage dependent tissue injury. Increased FXR expression was observed in the lungs of mice treated with ozone (0.8 ppm, 3 h); proinflammatory Ly6CHi macrophages were also increased, along with expression of iNOS and TLR4. Loss of FXR resulted in increases in Ly6CHi macrophages and prolonged upregulation of iNOS and TLR4; conversely, anti-inflammatory YM1+ macrophages were decreased, while Ly6CLo macrophages were increased. Changes in lung macrophage populations in FXR-/- mice were linked to exacerbation of ozone toxicity, as measured by cytochrome b5 expression and more pronounced structural changes. These data suggest that FXR plays a role in limiting macrophage inflammatory responses to irritant induced lung injury. (NIH Grants: ES004738, ES005022, AR055073).
Regulation of lung macrophage activation following irritant-induced injury by farnesoid X receptor FXR / Francis, M.; Rutgers University, Usa Kipen H.; Rutgers University, Usa; Guo, G; Rutgers, University; Usa, ; Laskin, J; Rutgers, University; Usa, ; Laskin, D; Rutgers, University; Usa, ; Businaro, Rita. - ELETTRONICO. - (2016). (Intervento presentato al convegno Cell Symposium: 100 Years of Phagocytes tenutosi a Giardini Naxos nel 19th - 22nd September 2016).
Regulation of lung macrophage activation following irritant-induced injury by farnesoid X receptor FXR
BUSINARO, Rita
2016
Abstract
FXR is a nuclear receptor that negatively regulates the transcription factor, NFĸB and macrophage inflammatory responses. Herein, we analyzed the role of FXR in lung macrophage activation following exposure of mice to ozone, a pulmonary irritant known to cause macrophage dependent tissue injury. Increased FXR expression was observed in the lungs of mice treated with ozone (0.8 ppm, 3 h); proinflammatory Ly6CHi macrophages were also increased, along with expression of iNOS and TLR4. Loss of FXR resulted in increases in Ly6CHi macrophages and prolonged upregulation of iNOS and TLR4; conversely, anti-inflammatory YM1+ macrophages were decreased, while Ly6CLo macrophages were increased. Changes in lung macrophage populations in FXR-/- mice were linked to exacerbation of ozone toxicity, as measured by cytochrome b5 expression and more pronounced structural changes. These data suggest that FXR plays a role in limiting macrophage inflammatory responses to irritant induced lung injury. (NIH Grants: ES004738, ES005022, AR055073).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
