Details

Autor(en) / Beteiligte

• Chen, Hong-Guang
• Xie, Ke-Liang
• Han, Huan-Zhi
• Wang, Wei-Na
• Liu, Da-Quan
• Wang, Guo-Lin
• Yu, Yong-Hao

Titel

Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages

Ist Teil von

• International journal of surgery (London, England), 2013-01, Vol.11 (10), p.1060-1066

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Abstract Background Molecular hydrogen (H2 ) as a new medical gas has an anti-inflammatory effect. In the present study, we investigated whether heme oxygenase-1 (HO-1) contributes to the anti-inflammatory effect of H2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods RAW 264.7 macrophages were stimulated by LPS (1 μg/mL) with presence or absence of different concentrations of H2 . Cell viability and injury were tested by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and lactate dehydrogenase (LDH) release, respectively. The cell culture supernatants were collected to measure inflammatory cytokines [TNF-α, IL-1β, HMGB1 (high mobility group box-1) and IL-10] at different time points. Moreover, HO-1 protein expression and activity were tested at different time points. In addition, to further identify the role of HO-1 in this process, zinc protoporphyrin (ZnPP)-IX, an HO-1 inhibitor, was used. Results H2 treatment had no significant influence on cell viability and injury in normally cultured RAW 264.7 macrophages. Moreover, H2 treatment dose-dependently attenuated the increased levels of pro-inflammatory cytokines (TNF-α, IL-1β, HMGB1), but further increased the level of anti-inflammatory cytokine IL-10 at 3 h, 6 h, 12 h and 24 h after LPS stimulation. Furthermore, H2 treatment could also dose-dependently increase the HO-1 protein expression and activity at 3 h, 6 h, 12 h and 24 h in LPS-activated macrophages. In addition, blockade of HO-1 activity with ZnPP-IX partly reversed the anti-inflammatory effect of H2 in LPS-stimulated macrophages. Conclusions Molecular hydrogen exerts a regulating role in the release of pro- and anti-inflammatory cytokines in LPS-stimulated macrophages, and this effect is at least partly mediated by HO-1 expression and activation.