Molecular Mechanism of Barrier Function Changes of Epithelial Tight Junction in Allergic Rhinitis

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1. We examined the effect of histamine, leukotriene D4 (LTD4) and thrombin on the epithelial permeability to 14C labeled mannitol and albumin using Calu-3 cell lines. 10^<-6>M LTD4 did not change permeability to mannitol or albumin. On the other hand, histamine and 10^<-7>〜10^<-8> M thrombin significantly increased epithelial permeability to mannitol. Moreover, 10^<-4>M histamine significantly increased the passage of horseradish peroxidase across epithelial tight junction in guinea pig nose.2. Next we examined if histamine and thrombin can alter mRNA expression of tight junction proteins. We added histamine or vehicle to cultured human nasal epithelial cells and extracted RNA from them 4 hours later. After DNase treatment, mRNAs of β-actin and ZO-1 tight-junction protein were amplified by RT-PCR. Histamine significantly downregulated ZO-1 mRNA expression. This effect was blocked by pretreatment with mepyramine, an H1 receptor antagonist. Next we examined the effect of thrombin on the tight junction proteins mRNAs expression in cultured epithelial cells. Thrombin significantly decreased ZO-1 mRNA expression of the cells, but had no effect on the expression of occludin or claudin mRNAs. The reduction of ZO-1 mRNA by histamine and thrombin may cause increased permeability of the mucosa during allergic reactions in the nose.