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We assessed PAR expression and functionality in human primary bronchial fibroblasts (HPBFs) before assessing PAR2-mediated HPBF proliferation, cytokine production, and adhesion molecule expression. RT-PCR and flow cytometry demonstrated that HPBFs express hPAR1, hPAR2, and hPAR3, but not hPAR4. Intracellular calcium signaling in HPBFs in response to PAR agonists showed that only hPAR1 and hPAR2 were functional receptors. We used the MTT assay to assess HPBF proliferation. Of the PAR2 agonist proteinases or selective PAR2-activating peptides (PAR2-APs) tested, none stimulated HPBF proliferation, whereas thrombin was a HPBF growth factor. mRNA for IL-8 and granulocyte colony-stimulating factor (G-CSF) was upregulated after addition of SLIGKV-NH2 when assessed by RT-PCR. No significant increase in G-CSF or IL-8 protein was detected. Trypsin stimulated IL-8 and G-CSF release from HPBF in a time- and dose-dependent manner. Leupeptin and soya trypsin inhibitor abrogated trypsin-stimulated cytokine release, indicating a requirement for trypsin's proteolytic activity. Trypsin and SLIGKV-NH2 stimulated an increase in VCAM-1 expression at 12 h after treatment, which declined thereafter. PAR2-driven upregulation of VCAM-1 cell surface expression and the release of IL-8 and G-CSF from bronchial fibroblasts may be important in promoting neutrophilic airways inflammation.<\/jats:p>","DOI":"10.1165\/rcmb.2005-0362oc","type":"journal-article","created":{"date-parts":[[2006,2,23]],"date-time":"2006-02-23T20:59:50Z","timestamp":1140728390000},"page":"133-141","source":"Crossref","is-referenced-by-count":27,"title":["Proteinase-Activated Receptor2 Agonists Upregulate Granulocyte Colony-Stimulating Factor, IL-8, and VCAM-1 Expression in Human Bronchial Fibroblasts"],"prefix":"10.1093","volume":"35","author":[{"given":"Rithwik","family":"Ramachandran","sequence":"first","affiliation":[{"name":"Respiratory Medicine, Division of Academic Medicine, Post Graduate Medical Institute of the University of Hull in association with the Hull York Medical School, East Yorkshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyn 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