[Regulation of gene expression of L-histidine decarboxylase and histamine N-methyl-transferase, and its relevance to the pathogenesis of bronchial asthma].

Histamine plays a critical role in the pathogenesis of bronchial asthma. L-Histidine decarboxylase (HDC) is a unique enzyme in mammals which catalyzes histamine formation from L-histidine. Human HDC consists of 662 amino acid residues (M(r) 74,178) and its 2.4 kb mRNA was expressed in stomach, brain and lung. In particular, the level of HDC mRNA was elevated in asthmatic patients. The HDC gene localizes in chromosome 15 and is composed of 12 exons spanning 24 kb. In the promoter area of HDC, 4 GATA and 6 LBP-1 possible binding sites were identified, suggesting that several transcriptional factors may regulate HDC gene. Histamine N-methyltransferase (HMT) is a principal enzyme of histamine degradation in the airway. Human HMT consists of 292 amino acid residues (M(r) 33,279) and its 1.6 kb mRNA was expressed in nasal polyp, kidney and lung. Particularly, HMT mRNA localized in airway epithelium. HMT gene localizes chromosome 1 p32 and its gene structure was partially analyzed. A specific inhibitor of HMT, SKF91488 augments airway contractile response to histamine, suggesting that the level of HMT activity is one of the important factors determining airway hyperresponsiveness. Viral infection, NO2 inhalation and allergen challenge modulate HMT activity in airway, which is important in the pathogenesis of asthma.