Open AccessCyclic peptide * CRRETAWAC * attenuates fibronectin‐induced cytokine secretion of human airway smooth muscle cells by inhibiting FAK and p38 MAPK
Author(s) -
Chu Mengdi,
Ji Jiani,
Cao Wenhao,
Zhang Huojun,
Meng Dan,
Xie Bangruan,
Xu Shuyun
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13174
Subject(s) - fibronectin , secretion , integrin , eotaxin , microbiology and biotechnology , cytokine , p38 mitogen activated protein kinases , mapk/erk pathway , focal adhesion , biology , phosphorylation , chemistry , endocrinology , cell , chemokine , immunology , extracellular matrix , inflammation , biochemistry
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 MAPK s including p38, ERK 1/2 and JNK 1/2 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.