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J Allergy Clin Immunol. 2007 Jun;119(6):1398-407. Epub 2007 Apr 6.

Connective tissue growth factor expression is regulated by histamine in lung fibroblasts: potential role of histamine in airway remodeling.

Author information

  • 1University Children's Hospital, W├╝rzburg, Germany. kunzmann_s@kinderklinik.uni-wuerzburg.de

Abstract

BACKGROUND:

In the inflamed lung of allergic asthma, an aberrant injury-repair response is accompanied by structural changes in the airway, known as airway remodeling. TGF-beta and its downstream mediator connective tissue growth factor (CTGF) are playing a key role in these processes, resulting in irreversible airway remodelling.

OBJECTIVE:

As histamine is a key mediator of allergic reactions, we investigated whether histamine is involved in airway remodeling.

METHODS:

The effect of histamine and TGF-beta1 on proliferation of lung fibroblast cells IMR-90 was studied by [(3)H]-thymidine proliferation assay. The regulation of CTGF by histamine and TGF-beta1 in lung fibroblasts was analyzed by RT-PCR, real-time PCR, Western blot analysis, and promoter analysis and characterized by specific histamine-receptor antagonists.

RESULTS:

Histamine and TGF-beta1 enhanced proliferation of lung fibroblast cells IMR-90. Both induced CTGF mRNA and protein expression with different time kinetics. Whereas TGF-beta1 induced maximal CTGF expression after 12 hours (347% +/- 23%), histamine-induced maximal CTGF expression was lower and delayed (maximum expression of 204% +/- 11% after 48 hours). Histamine and TGF-beta1 stimulated the CTGF promoter and the TGF-beta-response element in the CTGF promoter. The histamine-induced CTGF expression was mediated through the histamine receptor (HR1) and could be completely abolished by TNF-alpha.

CONCLUSIONS:

These findings demonstrate that histamine plays a potential role in the induction of airway remodeling mediated by the induction of lung fibroblasts proliferation and CTGF expression.

CLINICAL IMPLICATIONS:

This mechanism could be important for prophylactic strategies aiming at airway remodeling and could be a new indication for antihistamine treatment.

PMID:
17412405
[PubMed - indexed for MEDLINE]
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