Intranasal levels of lead as an exacerbation factor for allergic rhinitis in humans and mice.

BACKGROUND: Air pollutants are suspected to affect pathological conditions of allergic rhinitis (AR). OBJECTIVES: After detecting Pb (375 µg/kg) in Japanese cedar pollen, the effects of intranasal exposure to Pb on symptoms of AR were investigated. METHODS: Pollen counts, subjective symptoms, and Pb levels in nasal epithelial lining fluid (ELF) were investigated in 44 patients with Japanese cedar pollinosis and 57 controls from preseason to season. Effects of intranasal exposure to Pb on symptoms were confirmed by using a mouse model of AR. RESULTS: Pb levels in ELF from patients were >40% higher than those in ELF from control subjects during the pollen season but not before the pollen season. Pb level in ELF was positively associated with pollen counts for the latest 4 days before visiting a hospital as well as scores of subjective symptoms. Intranasal exposure to Pb exacerbated symptoms in allergic mice, suggesting Pb as an exacerbation factor. Pb levels in ELF and nasal mucosa in Pb-exposed allergic mice were higher than those in Pb-exposed nonallergic mice, despite intranasally challenging the same amount of Pb. Because the increased Pb level in the nasal mucosa of Pb-exposed allergic mice was decreased after washing the nasal cavity, Pb on the surface of but not inside the nasal mucosa may have been a source of increased Pb level in ELF of allergic mice. CONCLUSIONS: Increased nasal Pb level partially derived from pollen could exacerbate subjective symptoms of AR, indicating Pb as a novel hazardous air pollutant for AR.

Cytochrome P450 genes play central roles in transcriptional response by keratinocytes to a high-voltage alternating current electric field.

The endogenous electric field (EF) of skin wounds plays an important role in the biological processes that underlie wound healing. Treatments that modulate wound-EFs promote healing. However, the mechanism(s) that underlie this effect remain unclear. Agilent-based microarrays were used to determine the transcriptomes of the keratinocyte line HaCaT, normal human dermal fibroblasts, and the human dermal endothelial cell line HMEC-1 before and after high-voltage alternating current (AC)-EF (14,000 V, 90 Hz) treatment. The keratinocytes had the most genes whose transcription was altered by EF. They included the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1, HMOX1, EREG, DUSP5, and SLC7A11 (all upregulated), and DOCK8, ABCC6, and CYP26A1 (all downregulated). As shown by transcriptional-network analysis, all three CYP genes played central roles in the EF-induced changes in keratinocyte transcriptome. To the best of our knowledge, this is the first study that demonstrates that CYP genes play a key role in the transcriptional responses of human keratinocytes to EF treatment. Further investigations into the effects of EF on wound healing, aging, and regenerative medicine are likely to yield promising results.