The influence of Polycyclic aromatic hydrocarbons in FcgRIIb -/- lupus mice

Abstract

The activation of aryl hydrocarbon receptor (Ahr) through polycyclic aromatic hydrocarbons (PAHs), the major components of particulate matter at 2.5 micron (PM2.5) in the polluted air, might aggravate inflammation and lupus activity. Hence, 1,4-chrysenequinone (1,4-CQ), a substance in the PAHs group, was tested in a lupus model from FcgRIIb deficiency (FcgRIIb-/-) using macrophages and mice.

Although the activation by 1,4-CQ alone was unable to induce inflammation, the pre-conditioning by lipopolysaccharide (LPS), a representative inflammatory-activator, before 1,4-CQ (LPS/1,4-CQ) induced more predominant inflammation in macrophages when compared with LPS or 1,4-CQ activation alone as determined by supernatant cytokines (TNF-α, IL-6 and IL-10). Additionally, the activation in FcgRIIb-/- macrophages induce the more prominent inflammation than the wild-type (WT) cells, as determined by supernatant cytokines (TNF-α, IL-6 and IL-10), expression of inflammatory-genes (NF-κB, aryl hydrocarbon receptor, iNOS, IL-1β) and cell-surface CD-86, possibly due to the lack of inhibitory-FcgRIIb. Moreover, 8-wk-administration of 1,4-CQ started in 8-week-old FcgRIIb-/- mice, a genetic-prone lupus model, enhanced lupus severity as indicated by anti-dsDNA, serum creatinine, proteinuria, endotoxemia, and gut-leakage (FITC-dextran).

In conclusion, the Ahr activation by PAHs worsened lupus severity in FcgRIIb-/- mice possibly through the increased inflammatory responses due to the loss of the inhibitory-FcgRIIb. These data suggest that patients with lupus are possibly more vulnerable to the air pollution than the healthy persons.