Cyclic peptide *CRRETAWAC* attenuates fibronectin-induced cytokine secretion of human airway smooth muscle cells by inhibiting FAK and p38 MAPK
| Autor: | Meng-di Chu, Dan Meng, Wenhao Cao, Huojun Zhang, Shuyun Xu, Bangruan Xie, Jiani Ji |
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| Rok vydání: | 2017 |
| Předmět: |
Chemokine CCL11
Male 0301 basic medicine medicine.medical_specialty p38 mitogen-activated protein kinases Myocytes Smooth Muscle Respiratory System Gene Expression Peptide Peptides Cyclic p38 Mitogen-Activated Protein Kinases 03 medical and health sciences Western blot fibronectin Internal medicine medicine Humans Secretion Amino Acid Sequence Phosphorylation Chemokine CCL5 Cells Cultured Aged chemistry.chemical_classification biology medicine.diagnostic_test Original Articles Cell Biology asthma Middle Aged respiratory system airway smooth muscle Fibronectins respiratory tract diseases Cell biology Fibronectin 030104 developmental biology Endocrinology chemistry Focal Adhesion Kinase 1 biology.protein Cytokines Molecular Medicine Original Article Female Cytokine secretion integrin α5β1 Antibody |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| DOI: | 10.1111/jcmm.13174 |
| Popis: | α5β1 integrin is highly expressed in airway smooth muscle cells and mediate the adhesion of airway smooth muscle cells to fibronectin to regulate airway remodelling in asthma. This study aimed to investigate the effects of synthetic cyclic peptide *CRRETAWAC* on fibronectin‐induced cytokine secretion of airway smooth muscle cells and the underlying mechanism. Human airway smooth muscle cells were isolated and treated with fibronectin, IL‐13, *CRRETAWAC* peptide, α5β1 integrin‐blocking antibody, FAK inhibitor or p38 MAPK inhibitor. The transcription and secretion of eotaxin‐1 and RANTES were detected by real‐time PCR and ELISA, respectively. The phosphorylation of FAK and MAPKs including p38, ERK1/2 and JNK1/2 was detected by Western blot analysis. The transcription and secretion of eotaxin‐1 and RANTES increased in airway smooth muscle cells cultured in fibronectin‐coated plates. However, α5β1 integrin‐blocking antibody, *CRRETAWAC* peptide, FAK inhibitor or p38 MAPK inhibitor significantly reduced mRNA levels and the secretion of eotaxin‐1 and RANTES in airway smooth muscle cells cultured in fibronectin‐coated plates. In addition, the phosphorylation of FAK and p38 MAPK was significantly increased in airway smooth muscle cells cultured in fibronectin‐coated plates compared to the cells cultured in uncoated plates and was significantly reduced in airway smooth muscle cells treated with *CRRETAWAC* peptide. Fibronectin induces cytokine synthesis and secretion of airway smooth muscle cells. Peptide *CRRETAWAC* antagonizes fibronectin‐induced cytokine synthesis and secretion of airway smooth muscle cells via the inhibition of FAK and p38 MAPK, and is a potential agent for the therapy of asthma. |
| Databáze: | OpenAIRE |
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