关键词: Differentiation Fibrocytes IL-4 Serum amyloid P Store-operated Ca(2+) channels

Mesh : Calcium / metabolism Calcium Channel Agonists / pharmacology Calcium Channel Blockers / pharmacology Calcium Signaling / drug effects Cell Differentiation / drug effects Cells, Cultured Dose-Response Relationship, Drug Humans Imidazoles / pharmacology Interleukin-4 / pharmacology Mesenchymal Stem Cells / drug effects metabolism pathology Neoplasm Proteins / drug effects metabolism ORAI1 Protein / drug effects metabolism Serum Amyloid P-Component / pharmacology Stromal Interaction Molecule 1 / drug effects metabolism Time Factors

来  源:   DOI:10.1016/j.pharep.2017.07.005   PDF(Sci-hub)

Abstract:
BACKGROUND: Circulating fibrocytes (CFs) have been shown to participate in subepithelial fibrosis of asthma with chronic airflow limitation by acting as an important source of fibroblasts deposited beneath airway epithelia. Serum amyloid P (SAP) is an innate inhibitor of fibrocytes differentiation. Store-operated Ca2+ entry (SOCE) is the major Ca2+ influx of non-excitable cells. In this study, the role of SOCE in the regulation of fibrocytes differentiation and the effects of Th2 cytokine IL-4 and SAP on SOCE of fibrocytes were investigated.
METHODS: Peripheral blood mononuclear cells or monocytes were cultured in serum-free medium for 7days to differentiate into fibrocytes; the expression of SOC channels was determined with PCR, SOCE was measured with Ca2+ fluorescence imaging.
RESULTS: IL-4 significantly promoted monocyte derived fibrocytes differentiation in vitro. It also increased both SOCE which was induced by thapsigargin or UTP and molecules STIM1 and Orai1 which were related to expression of SOC channels in fibrocytes. Fibrocytes differentiation induced by IL-4 and SOC channels activity could be inhibited by SOC channel blocker SKF-96365. As expected, SAP significantly inhibited IL-4-induced differentiation of fibrocytes, the activity of SOCE and the expression of STIM1 and Orai1 in IL-4-treated fibrocytes.
CONCLUSIONS: IL-4 and SAP reversely regulates cultured fibrocytes differentiation in vitro by respectively promoting or inhibiting the expression and activity of SOC channels in fibrocytes.
摘要:
暂无翻译
公众号