Regulatory effect of histamine H1 receptor antagonist on the expression of messenger RNA encoding CC chemokines in the human nasal mucosa.
BACKGROUND
Allergic rhinitis is characterized by tissue accumulation of inflammatory cells. CC chemokines, including monocyte chemotactic protein (MCP) 1, MCP-3, RANTES, and eotaxin, are thought to play an important role in inducing selective recruitment of these cells to the allergic inflammatory site. Furthermore, MCPs have been indicated as histamine-releasing factors. Histamine is an important mediator in the pathogenesis of nasal allergy. The regulation of histamine may have a role in the management of allergic inflammation.


OBJECTIVE
The objectives of this study were to investigate the expression of MCP-1, MCP-3, RANTES, and eotaxin in the nasal mucosa of patients with allergic rhinitis and to clarify the effect of histamine and antihistamine on the regulation of the expression of these CC chemokines.


METHODS
By using a semiquantitative reverse transcriptase PCR technique, the numbers of copies of messenger RNA encoding MCP-1, MCP-3, RANTES, and eotaxin were measured in explant cultures of human nasal mucosa. In culture medium, specific antigen or histamine was added. Furthermore, the effect of preincubation with the antihistamine carebastine was estimated.


RESULTS
Mite antigen (1:2 x 10(4) dilution) and histamine (10(-4) to 10(-3) mol/L) upregulated the messenger RNA expression of these CC chemokines at 3- to 10-fold increases. Carebastine (10(-7) to 10(-6) mol/L) inhibited this upregulation.


CONCLUSIONS
Our results suggest that histamine may induce CC chemokine production in the nasal mucosa of patients with allergic rhinitis. This indicates that there may be a prolonged inflammatory cycle in the histamine-MCP axis in allergic rhinitis. The regulation of histamine-CC chemokine interaction could lead to new therapeutic approaches in the treatment of nasal allergy.
Fujikura
T
T
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
Shimosawa
T
T
Yakuo
I
I
D000328:Adult; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D002090:Butyrophenones / Q000494:pharmacology; D019742:Chemokines, CC / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008925:Mites / Q000276:immunology; D009297:Nasal Mucosa / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
D000941:Antigens; D002090:Butyrophenones; D019742:Chemokines, CC; D006634:Histamine H1 Antagonists; D010880:Piperidines; D012333:RNA, Messenger; C058251:carebastine; D006632:Histamine