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The article discusses the role of hypoxia and aryl hydrocarbon receptor (AhR) in cystic fibrosis (CF) and their potential for anti-inflammatory therapy. Hypoxia contributes to ineffective airway inflammation in CF and inhibiting HIF-1α could impair essential immune functions. The article demonstrates an interferential cross-talk between the AhR and HIF-1α signaling pathways in murine and human CF, where HIF-1α induction impairs the normal AhR response. However, AhR agonism can prevent hypoxia-driven inflammation, restore immune homeostasis, and improve lung function. This study highlights the contribution of environmental factors such as infections in CF disease progression and suggests using hypoxia:xenobiotic receptor cross-talk for anti-inflammatory therapy in CF.
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