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- Title
ARYL HYDROCARBON RECEPTOR (AhR) LIMITS THE INFLAMMATORY IMPACT OF EXTRACT OF REFERENCE DIESEL EXHAUST PARTICLES IN HUMAN LUNG EPITHELIAL A549 CELLS.
- Authors
Vázquez-Gómez, Gerardo; Karasová, Martina; Tylichová, Zuzana; Kabatková, Marketa; Hampl, Aleš; Matthews, Jason; Neča, Jiří; Ciganek, Miroslav; Machala, Miroslav; Vondráček, Jan
- Abstract
The aryl hydrocarbon receptor (AhR) is well known for its detoxification/bioactivation role. However, it has been suggested to participate also in the control of inflammatory responses. Diesel exhaust particles (DEP) are known to induce inflammation in respiratory tract. Here, we used standard reference mixture of diesel exhaust particles (SRM1650b) in order to evaluate the functional role of the AhR (using wild-type and AhR-deficient A549 lung epithelial cells) in the control of inflammatory responses towards DEP-associated pollutants. We compared their effects with those of pro-inflammatory cytokines, such as IL-1β. We found that the induction of cyclooxygenase-2 (and secretion of prostaglandins), as well as expression of pro-inflammatory cytokines, were notably higher in the AhR-deficient A549 cells, when exposed to inflammatory cytokines. Both crude organic extract of SRM1650b and its polar fraction induced an increased inflammatory response in AhR KO cells, including the induction of COX-2, TNFα, CXCL8 and IL-6 mRNAs. Our further experiments have identified increased nuclear factor-κB (NF-κB) activity to contribute to the exacerbated inflammatory response in the AhR-deficient A549 cells. Thus, the interplay of AhR and NF-κB signaling may modulate responses of lung epithelial cells towards complex mixtures of organic pollutants, such as those associated with DEP.
- Subjects
INFLAMMATION; EPITHELIAL cells; CYTOKINES
- Publication
Military Medical Science Letters / Vojenské zdravotnické Listy, 2022, Vol 91, p84
- ISSN
0372-7025
- Publication type
Abstract