Abstract
Polycyclic aromatic hydrocarbons (PAHs) are a group of chemical compounds found in urbane air, which have been suggested to contribute to pulmonary diseases by modulating pro inflammatory responses. The relative potency of the various PAHs and signaling pathways behind the PAH induced inflammation are not well known. Therefore, we wanted to assess if various PAHs modulates the aryl hydrocarbon receptor (AhR) and the possible importance of AhR in altering pro-inflammatory responses. We exposed human bronchial epithelial cells (BEAS 2B) to eight different PAHs; phenanthrene, 1 methylphenanthrene (1 MP), fluoranthene, pyrene, 1 nitropyrene (1 NP), β naphthoflavone (β NF), benzo[a]pyrene (B[a]P), and benzo[e]pyrene (B[e]P). All the PAHs modulated AhR through altering CYP1A1 expression. B[a]P, B[e]P, and phenanthrene had agonistic properties towards AhR, whereas the other PAHs (1-MP, fluoranthene, pyrene, and 1 NP) had antagonistic properties. Notably, the agonistic/antagonistic abilities seemed to be partly concentration-dependent. The tested PAHs generally had none or marginal effects on the IL 6 release. In contrast, they did not markedly change the CXCL8 release. When the cells were primed with the Toll-like receptor 3 (TLR3) agonist polyinosinic:polycytidylic (Poly I:C), which mimics a viral infection, pyrene slightly increased the IL 6 and CXCL8 release, but the other PAHs did not cause any marked changes. However, there were some variations between the different experiments that may have masked the possible effects. Inhibiting AhR by treating the unprimed and primed cells with the AhR antagonist CH223191 illustrated that cytokine release in both unprimed and primed cells could be dependent on AhR activity. In contrast, inhibiting AhR caused no observable effect on IL 6 and CXCL8 expression in unprimed cells. Lastly, pyrene and B[a]P did not increase Ca2+ release as evaluated using Cal 520 AM dye and measuring fluorescence using a microplate fluorescence reader. However, it should be noted that the used method may not be sensitive enough to detect possible responses. This study elucidates that the PAHs may modulate the classical genomic pathway of AhR. However, using the present experimental model, their effects on pro-inflammatory responses seem to be marginal, were cytokine release appeared to be dependent on AhR activity, while the synthesis was unaffected.