In vivo synergistic enhancement of MIF-mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1.
Summary
Inhaled human MIF induced hallmarks of acute lung injury in mice, while Arabidopsis MDL1 alone had no effect. Combined inhalation of MIF and MDL1 synergistically amplified neutrophil/monocyte infiltration and pro-inflammatory gene expression, indicating cross-kingdom potentiation of MIF-driven pulmonary inflammation.
Key Findings
- Human MIF inhalation induced ALI features in mice across multiple assays (flow cytometry, immunofluorescence, RT-qPCR, ELISA).
- MDL1 (Arabidopsis MIF ortholog) alone did not provoke lung injury.
- Combined MIF + MDL1 synergistically increased neutrophil and monocytic infiltration and upregulated pro-inflammatory cytokine genes.
- Data demonstrate cross-kingdom potentiation of MIF-driven inflammation in vivo.
Clinical Implications
Immediate practice change is unlikely. Findings support therapeutic targeting of the MIF axis in ALI/ARDS and raise awareness that exogenous plant-derived proteins may modulate human inflammatory pathways.
Why It Matters
Reveals a novel, cross-kingdom mechanism that intensifies MIF-mediated lung inflammation, opening new avenues for understanding environmental and biological modulators of ALI/ARDS.
Limitations
- Preclinical mouse study without human validation
- Mechanistic receptor/interaction details and exposure relevance to humans remain undefined
Future Directions
Define molecular mechanisms of MIF–MDL1 interaction, assess human exposure contexts, and test MIF pathway inhibitors in ALI models.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical in vivo animal study elucidating mechanism
- Study Design
- OTHER