# Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages.
> LPS刺激RAW 264.7マクロファージにおける分子状水素の抗炎症効果とヘムオキシゲナーゼ-1の関与


## Abstract

Using LPS-stimulated RAW 264.7 macrophages, this in vitro study examined whether heme oxygenase-1 (HO-1) participates in the anti-inflammatory actions of molecular hydrogen (H2). H2 at various concentrations did not affect cell viability or lactate dehydrogenase release under normal culture conditions. Following LPS stimulation (1 μg/mL), H2 dose-dependently reduced pro-inflammatory cytokines TNF-α, IL-1β, and HMGB1 while elevating the anti-inflammatory cytokine IL-10 at 3, 6, 12, and 24 hours. Concurrently, H2 increased HO-1 protein expression and enzymatic activity in a dose-dependent manner. Pharmacological inhibition of HO-1 with zinc protoporphyrin-IX (ZnPP-IX) partially reversed these anti-inflammatory effects, indicating that HO-1 induction is at least partly responsible for H2-mediated cytokine modulation in activated macrophages.

### Mechanism

H2 upregulates HO-1 protein expression and activity in LPS-activated macrophages, leading to suppression of pro-inflammatory cytokines (TNF-α, IL-1β, HMGB1) and elevation of IL-10. Blocking HO-1 with ZnPP-IX partially abolishes these effects, confirming HO-1 as a key mediator.

## Bibliographic

- **Authors**: Chen H, Xie K, Han H, Wang WS, Liu DQ, Wang G, et al.
- **Journal**: Int J Surg
- **Year**: 2013
- **PMID**: [24148794](https://pubmed.ncbi.nlm.nih.gov/24148794/)
- **DOI**: [10.1016/j.ijsu.2013.10.007](https://doi.org/10.1016/j.ijsu.2013.10.007)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 24148794. https://h2-papers.org/en/papers/24148794
> **Source**: PubMed PMID [24148794](https://pubmed.ncbi.nlm.nih.gov/24148794/)