title: Induction of monocyte chemoattractant protein-1 release from A549 cells by agonists of protease-activated receptor-1 and -2.
abstract: Hypersecretion of cytokines and serine proteases has been observed in asthma. However, the influence of proteases and protease-activated receptors (PARs) on monocyte chemoattractant protein-1 (MCP-1) release from airway epithelial cells remains largely unknown. In the present study, A549 cells were challenged with agonists of PARs, and levels of MCP-1 released in the supernatant and mRNA expression were examined by ELISA and real time polymerase chain reaction (PCR), respectively. The results show that thrombin, tryptase, elastase and trypsin induced an up to 6.5-, 1.8-, 1.6-, and 3.1-fold increase in MCP-1 release from A549 cells, respectively, following a 16-h incubation period. The protease-induced secretion of MCP-1 can be abolished by specific protease inhibitors. Agonist peptides of PAR-1 and PAR-2 stimulate MCP-1 secretion up to 15- and 12.7-fold, respectively. Real-time PCR showed that MCP-1 mRNA is up-regulated by the serine proteases tested and by agonist peptides of PAR-1 and PAR-2. In conclusion, serine proteases can stimulate MCP-1 release from A549 cells possibly through a PARs-related mechanism, suggesting that they are likely to contribute to MCP-1-related airway inflammatory disorders in man.
authors.affiliation: Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Yi
authors.forename: Yanshan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Shaoheng
authors.initials: S
authors.lastname: He
mesh_terms: D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D009842:Oligopeptides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D014357:Trypsin; D013917:Thrombin; D053802:Tryptases