Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis.
Toxicol Appl Pharmacol
; 288(2): 152-60, 2015 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-26163174
ABSTRACT
BACKGROUND:
Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. METHODS ANDRESULTS:
Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the followingresults:
1) SiO2 treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO2-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO2-induced increase in cell migration.CONCLUSION:
These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO2. CCR2 was also up-regulated in response to SiO2, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO2-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
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Silicose
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Movimento Celular
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Quimiocina CCL2
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Fibroblastos
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Pulmão
Limite:
Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China