Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation
SY Qin, RH Du, SS Yin, XF Liu, GL Xu, W Cao - Inflammation Research, 2015 - Springer
SY Qin, RH Du, SS Yin, XF Liu, GL Xu, W Cao
Inflammation Research, 2015•SpringerIntroduction Carbon monoxide (CO) released from CORM-2 has anti-inflammatory function,
but the critical molecule mediating the inflammation inhibition has not been elucidated.
Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating
host defense against oxidative stress and inflammation-related disorders. In this study we
use Nrf2 knockout mice to determine the role of Nrf2 in mediating the CO anti-inflammatory
action. Methods We compared CORM-2's inhibiting effect on pro-inflammatory cytokine …
but the critical molecule mediating the inflammation inhibition has not been elucidated.
Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating
host defense against oxidative stress and inflammation-related disorders. In this study we
use Nrf2 knockout mice to determine the role of Nrf2 in mediating the CO anti-inflammatory
action. Methods We compared CORM-2's inhibiting effect on pro-inflammatory cytokine …
Introduction
Carbon monoxide (CO) released from CORM-2 has anti-inflammatory function, but the critical molecule mediating the inflammation inhibition has not been elucidated. Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating host defense against oxidative stress and inflammation-related disorders. In this study we use Nrf2 knockout mice to determine the role of Nrf2 in mediating the CO anti-inflammatory action.
Methods
We compared CORM-2’s inhibiting effect on pro-inflammatory cytokine expressions (TNF-α, IL-1β and IL-6 and iNOS) in primary peritoneal macrophages, mouse liver and brain tissues from Nrf2+/+ and Nrf2−/− mice. We further assayed the inflammatory cell infiltration in both liver and brain tissues of the Nrf2+/+ and Nrf2−/− mice. Finally, we examined CORM’s influence on mouse mortality in a mouse sepsis model.
Results
Our results showed that CORM-2 dramatically inhibited the expression of pro-inflammatory cytokines in Nrf2+/+ mice, but not in Nrf2−/− mice. Furthermore CORM-2 substantially decreased LPS-induced mouse mortality of Nrf2+/+ mice, but not of Nrf2−/− mice.
Conclusion
We conclude that Nrf2 is indispensable for CORM-2 inhibition of LPS-induced inflammation.
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