The Aryl Hydrocarbon Receptor Attenuates Acute Cigarette Smoke-Induced Airway Neutrophilia Independent of the Dioxin Response Element

• DOI: 10.3389/fimmu.2021.630427
• Publication Date: 2021-02-15T04:19:22Z
• Authors: Angela Rico de Souza; Hussein Traboulsi; Xinyu Wang; Jorg H. Fritz; David H. Eidelman; Carolyn J. Baglole
• Keywords: Neutrophilia

Cigarette smoke is a prevalent respiratory toxicant that remains leading cause of death worldwide. induces inflammation in the lungs and airways contributes to development diseases such as lung cancer chronic obstructive pulmonary disease (COPD). Due presence aryl hydrocarbon receptor (AhR) ligands cigarette smoke, activation AhR has been implicated driving this inflammatory response. However, we have previously shown suppresses smoke-induced inflammation, but mechanism by which achieves its anti-inflammatory function unknown. In study, use antagonist CH-223191 inhibit activity mice. After an acute (3-day) exposure, inhibition was associated with significantly enhanced neutrophilia response mimicking phenotype AhR-deficient We then used genetically-modified mouse strains express can bind ligand either cannot translocate nucleus or cognate element, show these features pathway are not required for suppress neutrophilia. Finally, using non-toxic endogenous FICZ, provide proof-of-concept attenuates inflammation. Collectively, results support importance mediating smoke. Further investigation precise mechanisms exerts protective functions may lead therapeutic agents treat people etiology, few options exist.