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

Abstract

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.

• Authors: SiYuan Qin, RongHui Du, ShaSha Yin, XinFeng Liu, GeLin Xu, Wangsen Cao
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 64 Issue 7 Pg. 537-48 (Jul 2015) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 26049867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Lipopolysaccharides
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Organometallic Compounds
• tricarbonyldichlororuthenium (II) dimer
• Carbon Monoxide

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Brain (drug effects, metabolism)
• Carbon Monoxide (pharmacology)
• Cytokines (biosynthesis)
• Female
• Inflammation (chemically induced, prevention & control)
• Lipopolysaccharides (antagonists & inhibitors, toxicity)
• Liver (drug effects, metabolism)
• Macrophages, Peritoneal (drug effects, metabolism)
• Mice
• Mice, Inbred ICR
• Mice, Knockout
• NF-E2-Related Factor 2 (drug effects, genetics, metabolism)
• Organometallic Compounds (pharmacology)
• RAW 264.7 Cells
• Sepsis (metabolism, pathology)