Journal Article

Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation

Qin, SiYuan, Liu, XinFeng, Cao, Wangsen, Xu, GeLin, Du, RongHui, Yin, ShaSha

2015

Overview

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.

• Publisher: Springer Basel,Springer Nature B.V
• Subject: Allergology / Animals / Anti-Inflammatory Agents, Non-Steroidal - pharmacology / Biomedical and Life Sciences / Biomedicine / Brain - drug effects / Brain - metabolism / Carbon Monoxide - pharmacology / Cytokines - biosynthesis / Dermatology / Female / Immunology / Inflammation - chemically induced / Inflammation - prevention & control / Lipopolysaccharides - antagonists & inhibitors / Lipopolysaccharides - toxicity / Liver - drug effects / Liver - metabolism / Macrophages, Peritoneal - drug effects / Macrophages, Peritoneal - metabolism / Mice / Mice, Inbred ICR / Mice, Knockout / Neurology / NF-E2-Related Factor 2 - drug effects / NF-E2-Related Factor 2 - genetics / NF-E2-Related Factor 2 - metabolism / Organometallic Compounds - pharmacology / Original Research Paper / Pharmacology/Toxicology / RAW 264.7 Cells / Rheumatology / Sepsis - metabolism / Sepsis - pathology