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Diesel exhaust particulates upregulate histamine receptor mRNA and increase histamine-induced IL-8 and GM-CSF production in nasal epithelial cells and endothelial cells

Authors


Terada Department of Otorhinolaryngology, Chiba University School of Medicine, 1-8-1, Inohana, Chiba City 260, Japan.

Abstract

Background

Histamine is the most important chemical mediator in the pathogenesis of nasal allergy. Diesel exhaust particulates (DEPs) are common air pollutants from diesel engine-powered car exhaust and cause chronic airway diseases. Recently we observed that the nasal reactivity to histamine was enhanced in diesel exhaust-exposed guinea-pigs. It was also revealed that epithelial cells and endothelial cells in the airway produce certain cytokines in response to histamine.

Objective

We examined the effects of DEP extract on the expression of histamine H1 receptor (H1R) mRNA in human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs), and on the production of IL-8 and GM-CSF induced by histamine.

Methods

HNECs and HMMECs were isolated from human nasal mucosa specimens. HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract. The change in the expression of H1R mRNA was then evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and the Southern blot analysis. To investigate the effects of DEP extract on the histamine-induced cytokine production, HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract for 3–24 h. After three washes with PBS, they were then incubated with 10−6 mol/L histamine for 24 h. The amounts of IL-8 and GM-CSF in the culture media were measured by enzyme-linked immunoabsorent assay.

Results

DEP extract increased the expression of H1R mRNA in both HNECs and HMMECs. The amount of IL-8 and GM-CSF, induced by histamine, was significantly higher in DEP extract pretreated HNECs and HMMECs than nontreated HNECs and HMMECs.

Conclusion

These results strongly suggest that DEP accelerates the inflammatory change by not only directly upregulating H1R expression but also increasing histamine-induced IL-8 and GM-CSF production.

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