# Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species.
> マクロファージにおける分子状水素のNLRP3インフラマソーム活性化抑制：ミトコンドリア活性酸素種を標的とした機序


## Abstract

In mouse macrophages stimulated with lipopolysaccharide (LPS), molecular hydrogen (H2) was found to substantially suppress NLRP3 inflammasome activation, a multi-protein complex governing interleukin-1β maturation. H2 achieved this by scavenging mitochondrial reactive oxygen species (mtROS). Two distinct downstream mechanisms were identified: first, mtROS elimination by H2 blocked NLRP3 deubiquitination, a non-transcriptional priming event triggered by LPS; second, H2 reduced the generation of oxidized mitochondrial DNA, thereby diminishing its interaction with NLRP3 and further attenuating inflammasome assembly. These findings provide the first mechanistic account of how H2 interferes with LPS-driven NLRP3 inflammasome signaling in macrophages, centered on mitochondria-targeted antioxidant activity.

### Mechanism

H2 scavenges mitochondrial ROS, thereby blocking NLRP3 deubiquitination and reducing oxidized mitochondrial DNA production; both effects converge to inhibit NLRP3 inflammasome assembly and IL-1β maturation in LPS-stimulated macrophages.

## Bibliographic

- **Authors**: Ren JD, Wu XB, Jiang R, Hao DP, Liu Y
- **Journal**: Biochim Biophys Acta
- **Year**: 2016
- **PMID**: [26488087](https://pubmed.ncbi.nlm.nih.gov/26488087/)
- **DOI**: [10.1016/j.bbamcr.2015.10.012](https://doi.org/10.1016/j.bbamcr.2015.10.012)
- **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 26488087. https://h2-papers.org/en/papers/26488087
> **Source**: PubMed PMID [26488087](https://pubmed.ncbi.nlm.nih.gov/26488087/)