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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor involved in redox homeostasis and in the response induced by oxidative injury. Nrf2 is present in an inactive state in the cytoplasm of cells. Its activation by internal or external stimuli, such as infections or pollution, leads to the transcription of more than 500 elements through its binding to the antioxidant response element. The lungs are particularly susceptible to factors that generate oxidative stress such as infections, allergens and hyperoxia. Nrf2 has a crucial protective role against these ROS. Oxidative stress and subsequent activation of Nrf2 have been demonstrated in many human respiratory diseases affecting the airways, including asthma and chronic obstructive pulmonary disease (COPD), or the pulmonary parenchyma such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Several compounds, both naturally occurring and synthetic, have been identified as Nrf2 inducers and enhance the activation of Nrf2 and expression of Nrf2-dependent genes. These inducers have proven particularly effective at reducing the severity of the oxidative stress-driven lung injury in various animal models. In humans, these compounds offer promise as potential therapeutic strategies for the management of respiratory pathologies associated with oxidative stress but there is thus far little evidence of efficacy through human trials. The purpose of this review is to summarize the involvement of Nrf2 and its inducers in ARDS, COPD, asthma and lung fibrosis in both human and in experimental models.

Introduction: While there is increasing evidence that it exists a link between asthma development, early life exposure to allergens like house dust mite (HDM) and the microbiome composition, the underlying mechanisms remain elusive. While Nucleotide-binding oligomerization domain 1 (NOD1) has been shown to regulate the gut microbiota composition, our previous findings showed that a Nod1 agonist used as a systemic adjuvant exacerbates ovalbumin-induced Th2-mediated allergic asthma and more recently that HDM-induced asthma is improved in Nod1-deficient mice. Aims and objectives: The aim of his study was to evaluate if the intestinal dysbiosis present in Nod1 deficient mice may modify HDM-induced pulmonary inflammation. Methods: The role of NOD1 was investigated in the HDM-induced asthma model, using Wild-Type, NOD1 deficient mice and Ripk2 deficient mice. Fecal transplantation of Nod1 deficient or WT mice into germfree (GF) mice was performed and HDM-induced asthma evaluated. We measured airway hyperreactivity, total and differential cell counts in bronchoalveolar lavage (BAL), Th2 cytokines and chemokines in lung protein extracts and total IgE levels in the serum. Results: Our results show that HDM-sensitized/challenged NOD1 and Ripk2 deficient mice exhibited less pulmonary inflammation when compared to the wild-type mice. However there was no difference between GF mice transplanted with either Nod1 deficient or WT microbiota. Conclusion: Our results suggest that NOD1-deficient dysbiosis is not responsible for decreasing allergic inflammation parameters and suggest that the allergen may directly activate NOD1 receptor.