PMID- 17280738 OWN - NLM STAT- MEDLINE DCOM- 20070517 LR - 20070320 IS - 0171-9335 (Print) IS - 0171-9335 (Linking) VI - 86 IP - 4 DP - 2007 Apr TI - Induction of monocyte chemoattractant protein-1 release from A549 cells by agonists of protease-activated receptor-1 and -2. PG - 233-42 AB - 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. FAU - Wang, Haiyan AU - Wang H AD - Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, China. FAU - Yi, Tingting AU - Yi T FAU - Zheng, Yanshan AU - Zheng Y FAU - He, Shaoheng AU - He S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070205 PL - Germany TA - Eur J Cell Biol JT - European journal of cell biology JID - 7906240 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Oligopeptides) RN - 0 (Protease Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Receptor, PAR-1) RN - 0 (Receptor, PAR-2) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.36 (Pancreatic Elastase) RN - EC 3.4.21.4 (Trypsin) RN - EC 3.4.21.5 (Thrombin) RN - EC 3.4.21.59 (Tryptases) SB - IM MH - Cell Line, Tumor MH - Chemokine CCL2/*biosynthesis/genetics MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Lung Neoplasms/metabolism/pathology MH - Oligopeptides/pharmacology MH - Pancreatic Elastase/metabolism MH - Protease Inhibitors/pharmacology MH - RNA, Messenger/biosynthesis MH - Receptor, PAR-1/agonists/*metabolism MH - Receptor, PAR-2/agonists/*metabolism MH - Respiratory Mucosa/*metabolism/pathology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Serine Endopeptidases/*metabolism/pharmacology MH - Thrombin/*metabolism/pharmacology MH - Time Factors MH - Trypsin/metabolism MH - Tryptases/metabolism MH - Up-Regulation EDAT- 2007/02/07 09:00 MHDA- 2007/05/18 09:00 CRDT- 2007/02/07 09:00 PHST- 2006/06/21 00:00 [received] PHST- 2006/10/27 00:00 [revised] PHST- 2006/12/04 00:00 [accepted] PHST- 2007/02/07 09:00 [pubmed] PHST- 2007/05/18 09:00 [medline] PHST- 2007/02/07 09:00 [entrez] AID - S0171-9335(06)00192-0 [pii] AID - 10.1016/j.ejcb.2006.12.003 [doi] PST - ppublish SO - Eur J Cell Biol. 2007 Apr;86(4):233-42. doi: 10.1016/j.ejcb.2006.12.003. Epub 2007 Feb 5.