Page 64 - ebook

[A. Biochemistry/Molecular Biology] A-32

Nrf2 activation by 2-methoxycinnamaldehyde attenuates

macrophage-proinflammatory responses via enhancing

autophagy flux

Minwook Shin¹ , Bo-Sung Kim²,³ , Jin-Yeong Kim²,³, Ki-Tae Ha²,³, Sung-Jin Bae³*
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¹RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester 01655, USA, ²Department of

Korean Medical Science, Pusan National University, Yangsan 50612, Korea, ³Korean Medical Research Center for

Healthy Aging, Pusan National University, Yangsan 50612, Korea

Inflammation is the body's response to infection, tissue damage, and cellular stress. A well-controlled inflammatory
response has a beneficial effect for recovery and maintainance of tissue homeostasis. The anti-inflammatory

response of 2-MCA has been already known; however, the mechanism underlying anti-inflammatory action was not
fully elucidated. It was confirmed that the LPS-stimulated production of TNF-α and NO was reduced by 2-MCA

treatment in murine BMM and RAW264.7 cells. To investigate the mechanism by which 2-MCA has anti-inflammatory
effects, MAPK, NF-κB, and AP-1 signaling pathways activated by LPS were examined. 2-MCA treatment did not

affect the MAPK, NF-κB, and AP-1 signaling pathways. However, 2-MCA increased the expression and nuclear
localization of Nrf2 in macrophages. Our result showed that 2-MCA increased the mRNA and protein levels of p62
and Lc3. 2-MCA increased the luciferase activity in RAW264.7 cells expressing Lc3-Luciferase fusion protein which

was designed for investigating autophagic flux. In addition, LPS-stimulated expression of Tnf-α and Nos2 was

reduced by 2-MCA treatment and reversed by autophagy inhibitors. In conclusion, 2-MCA treatment activates Nrf2
in macrophages, induces autophagy, and consequently reduces LPS-induced inflammatory responses. Thus, here
we suggest that anti-inflammatory effect of 2-MCA might be regulated by Nrf2-mediated autophagy.