title: Cyclic peptide *CRRETAWAC* attenuates fibronectin-induced cytokine secretion of human airway smooth muscle cells by inhibiting FAK and p38 MAPK.
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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.|Ningbo Medical Treatment Center, Lihuili Hospital, Ningbo, China.
authors.forename: Mengdi
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Huojun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Meng
authors.affiliation: Wuhan Medical Treatment Center, Hubei, China.
authors.forename: Bangruan
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Shuyun
authors.identifier: 0000-0002-2647-754X
authors.initials: S
authors.lastname: Xu
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012137:Respiratory System / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D054413:Chemokine CCL11; D018946:Chemokine CCL5; D016207:Cytokines; D005353:Fibronectins; D010456:Peptides, Cyclic; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases
keywords: airway smooth muscle; asthma; fibronectin; integrin α5β1