Bradykinin differentiates human lung fibroblasts to a myofibroblast phenotype via the B2 receptor

被引：36

作者：

Vancheri, C ^{[1
]}

Gili, E ^{[1
]}

Failla, M ^{[1
]}

Mastruzzo, C ^{[1
]}

Salinaro, ET ^{[1
]}

LoFurno, D ^{[1
]}

Pistorio, MP ^{[1
]}

La Rosa, C ^{[1
]}

Caruso, M ^{[1
]}

Crimi, N ^{[1
]}

机构：

[1] Univ Catania, Dept Internal & Specialist Med, Sect Resp Dis, I-95125 Catania, Italy

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2005年 / 116卷 / 06期

关键词：

remodeling; lung fibrosis; alpha-SMA; MAPK;

D O I：

10.1016/j.jaci.2005.09.025

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: The identification of factors mediating the transition of lung fibroblasts into myofibroblasts is considered fundamental in the comprehension of abnormal reparative processes. Bradykinin, a mediator known for its proinflammatory action, is able to induce cytokine production and contractility in fibroblast cultures. Objectives: In this study the ability of bradykinin to drive fibroblast into a myofibroblast phenotype at the cellular and molecular level was evaluated. Methods: alpha-Smooth muscle actin (alpha-SMA) expression and TGF-beta in bradykinin stimulated fibroblasts were tested by means of flow cytometry, Western blot, and RT-PCR. Cell proliferation and collagen production were evaluated by the colorimetric methylthiazol tetrazolium assay and sirius red assay, respectively. Which bradykinin receptor mediates the expression of alpha-SMA was evaluated using selective B1 and B2 blocking agents. Furthermore, the effect of bradykinin on extracellular signal-regulated kinase 1/2 phosphorylation was explored. Results: Bradykinin caused in lung fibroblasts a significant increase in alpha-SMA at the cellular and molecular level. The B2 receptor was held responsible for this effect because a specific receptor antagonist had entirely blocked this effect. Bradykinin was able to induce fibroblast proliferation and collagen production. Bradykinin significantly activated mitogen-activated protein kinase pathway by phosphorylating extracellular signal-regulated kinase 1/2, whereas PD98059, a specific inhibitor, was able to block myofibroblast induction. Although bradykinin induced an increase of TGF-beta on fibroblasts, the blockage of this cytokine did not alter alpha-SMA expression. Conclusion: The data support the hypothesis that bradykinin may be involved in bronchial remodeling and lung fibrosis beyond its well recognized proinflammatory activity, also suggesting a new potential therapeutic strategy to control altered reparatory processes.

引用

页码：1242 / 1248

页数：7

共 28 条

[1] A BRADYKININ ANTAGONIST MODIFIES ALLERGEN-INDUCED MEDIATOR RELEASE AND LATE BRONCHIAL RESPONSES IN SHEEP [J].