Abstract
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.
Highlights
Asthma is characterized by reversible airway obstruction and airway hyper-responsiveness that is associated with airway inflammation and airway remodelling [1, 2]
For cells cultured in plates precoated with fibronectin, IL-13 stimulated higher expression of eotaxin-1 and RANTES mRNA levels as well as the secretion of eotaxin-1 and RANTES compared with cells cultured in uncoated plates (P
As *CRRETAWAC* peptide could specially block the binding of Integrin a5b1 to fibronectin, we examined whether it inhibits IL-13dependent and fibronectin-induced cytokine production by airway smooth muscle cells (ASMCs)
Summary
Asthma is characterized by reversible airway obstruction and airway hyper-responsiveness that is associated with airway inflammation and airway remodelling [1, 2]. Two prominent pathological features of asthma are the increase of airway smooth muscle (ASM) mass and the deposition of extracellular matrix (ECM) proteins, which contribute to the development of airway inflammation and remodelling. The deposition of increased ECM proteins such as fibronectin and Integrins are a group of transmembrane heterodimeric proteins that mediate cell–cell and cell–ECM interactions. Eighteen a-subunits and eight b-subunits dimerize non-covalently to form at least 24 different integrin heterodimers with specific tissue distribution [8]. The extracellular domain of integrin recognizes short peptide sequence Arg-Gly-Asp (RGD), which presents in ECM proteins such as a 2017 The Authors.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
