Progress in Allergy Signal Research on Mast Cells:
Up-Regulation of Histamine Signal-Related Gene Expression in Allergy Model Rats

Abstract

Brown Norway allergy model rats sensitized to toluene 2,4-diisocyanate (TDI) were developed. Histamine H₁ receptor mRNA level was elevated in nasal mucosa of allergy model rats after the provocation with TDI, which was followed by H₁-receptor up-regulation. Elevation of histamine H₁ receptor mRNA was partially suppressed by d-chlorpheniramine and olopatadine, antihistamines. Histamine induced increase in histamine H₁ receptor gene expression in vitro, and the protein kinase C-δ isoform was suggested to mediate the gene expression. On the other hand, elevation of histamine H₁ receptor mRNA was completely suppressed by dexamethasone in allergy model rats. Provocation with TDI also induced mRNA elevation of histidine decarboxylase, a sole histamine-forming enzyme, followed by the increase of both HDC activity and histamine content in nasal mucosa of allergy model rats. HDC mRNA elevation and increase in both HDC activity and histamine level were almost completely suppressed by dexamethasone. These observations suggest that histamine H₁ receptor up-regulation and increase in histamine level play an important role in allergy through the regulation of histamine signaling.