BACKGROUND: The identification of factors mediating the transition of lungfibroblasts into myofibroblasts is considered fundamental in the comprehension ofabnormal reparative processes. Bradykinin, a mediator known for itsproinflammatory action, is able to induce cytokine production and contractilityin fibroblast cultures.OBJECTIVES: In this study the ability of bradykinin to drive fibroblast into amyofibroblast phenotype at the cellular and molecular level was evaluated.METHODS: alpha-Smooth muscle actin (alpha-SMA) expression and TGF-beta inbradykinin stimulated fibroblasts were tested by means of flow cytometry, Westernblot, and RT-PCR. Cell proliferation and collagen production were evaluated bythe 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 ofbradykinin on extracellular signal-regulated kinase 1/2 phosphorylation wasexplored.RESULTS: Bradykinin caused in lung fibroblasts a significant increase inalpha-SMA at the cellular and molecular level. The B2 receptor was heldresponsible for this effect because a specific receptor antagonist had entirelyblocked this effect. Bradykinin was able to induce fibroblast proliferation andcollagen production. Bradykinin significantly activated mitogen-activated proteinkinase 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 inbronchial remodeling and lung fibrosis beyond its well recognized proinflammatoryactivity, also suggesting a new potential therapeutic strategy to control alteredreparatory processes.

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

VANCHERI, CARLO;LO FURNO, DEBORA;CARUSO, MASSIMO;CRIMI, Nunzio
2005-01-01

Abstract

BACKGROUND: The identification of factors mediating the transition of lungfibroblasts into myofibroblasts is considered fundamental in the comprehension ofabnormal reparative processes. Bradykinin, a mediator known for itsproinflammatory action, is able to induce cytokine production and contractilityin fibroblast cultures.OBJECTIVES: In this study the ability of bradykinin to drive fibroblast into amyofibroblast phenotype at the cellular and molecular level was evaluated.METHODS: alpha-Smooth muscle actin (alpha-SMA) expression and TGF-beta inbradykinin stimulated fibroblasts were tested by means of flow cytometry, Westernblot, and RT-PCR. Cell proliferation and collagen production were evaluated bythe 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 ofbradykinin on extracellular signal-regulated kinase 1/2 phosphorylation wasexplored.RESULTS: Bradykinin caused in lung fibroblasts a significant increase inalpha-SMA at the cellular and molecular level. The B2 receptor was heldresponsible for this effect because a specific receptor antagonist had entirelyblocked this effect. Bradykinin was able to induce fibroblast proliferation andcollagen production. Bradykinin significantly activated mitogen-activated proteinkinase 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 inbronchial remodeling and lung fibrosis beyond its well recognized proinflammatoryactivity, also suggesting a new potential therapeutic strategy to control alteredreparatory processes.
2005
lung fibrosis; a-SMA; MAPK
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/32200
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