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Published in: Inflammation Research 5/2018

01-05-2018 | Original Research Paper

Luteolin activates ERK1/2- and Ca2+-dependent HO-1 induction that reduces LPS-induced HMGB1, iNOS/NO, and COX-2 expression in RAW264.7 cells and mitigates acute lung injury of endotoxin mice

Authors: Eun Jung Park, Young Min Kim, Hye Jung Kim, Ki Churl Chang

Published in: Inflammation Research | Issue 5/2018

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Abstract

Objective

Although luteolin has shown to have anti-inflammatory action, no report is available whether luteolin inhibits HMGB1 and protects acute lung injury (ALI) in endotoxin rodents. We hypothesized that HO-1 induction by luteolin might play a crucial role for inhibition of pro-inflammatory mediators including HMGB1 through MAPK signaling in LPS-induced RAW264.7 cells, and it ameliorates ALI of endotoxin mice.

Methods

The effects of luteolin on the production of pro-inflammatory mediators in LPS-activated RAW264.7 cells and LPS-injected mice were evaluated. The mechanisms were investigated using various signal inhibitors.

Results

Luteolin significantly increased HO-1 expression through ERK1/2 signaling in a time- and concentration-dependent manner. Indeed, luteolin inhibited pro-inflammatory mediators (HMGB1, iNOS/NO, COX-2, and NF-κB activity) in LPS-activated RAW264.7 cells. In addition, PD98059, an ERK1/2 inhibitor, treatment failed to inhibit production of these pro-inflammatory mediators by luteolin. Interestingly, luteolin augmented HO-1 induction through Ca2+ influx in RAW264.7 cells. Administration of luteolin significantly inhibited plasma HMGB1 level, and iNOS expression in the lung that resulted in a significant reduction of ALI in endotoxin mice that was reversed by a HO-1 inhibitor, ZnPPIX.

Conclusion

Therefore, we conclude that luteolin has a great potential for treatment of ALI and related diseases, where HMGB1 is a therapeutic target.
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Metadata
Title
Luteolin activates ERK1/2- and Ca2+-dependent HO-1 induction that reduces LPS-induced HMGB1, iNOS/NO, and COX-2 expression in RAW264.7 cells and mitigates acute lung injury of endotoxin mice
Authors
Eun Jung Park
Young Min Kim
Hye Jung Kim
Ki Churl Chang
Publication date
01-05-2018
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 5/2018
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-018-1137-8

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