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Erschienen in: Inflammation Research 5/2018

01.03.2018 | 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

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

Erschienen in: Inflammation Research | Ausgabe 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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Metadaten
Titel
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
verfasst von
Eun Jung Park
Young Min Kim
Hye Jung Kim
Ki Churl Chang
Publikationsdatum
01.03.2018
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 5/2018
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-018-1137-8

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