ArticleThe European respiratory journal2025
Particulate matter-related ITIH4 deficiency is associated with an emphysema phenotype of COPD through JNK-dependent and JNK-independent signalling.
Article in The European respiratory journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026Review
- From symptoms to mechanisms: multidimensional insights into cannabis smoke.The European respiratory journal · 2026Article
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14 authors.
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Abstract
backgroundProlonged exposure to airborne particulate matter (PM) is associated with emphysema and COPD; however, the precise underlying mechanism remains unclear. In a previous high-throughput screen, we identified inter-α-trypsin inhibitor heavy chain 4 (ITIH4) as a biomarker of long-term PM exposure. We hypothesised that ITIH4 is implicated in PM-related emphysema.
methodsWe investigated the association between ITIH4 expression and ambient PM exposure through a clinical cohort analysis (220 patients with COPD and 61 healthy participants) and
resultsThe COPD cohort studies revealed significant correlations between emphysema severity, ambient PM exposure and serum ITIH4 levels. In primary small airway epithelial cells from COPD patients with low basal levels of ITIH4, exposure to PM and oxidative stress led to increased apoptosis. However, ITIH4 overexpression significantly inhibited oxidative-stress-induced apoptosis in normal and COPD airway epithelial cells. Acute exposure to hydrogen peroxide resulted in the rapid degradation of ITIH4 protein with no effect on transcriptional level, although
conclusionsWe identified a novel pathogenetic mechanism involving ITIH4, where chronic exposure to air pollution induces or promotes emphysema.
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