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Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2002 Jun; Vol. 282 (6), pp. L1339-48. - Publication Year :
- 2002
-
Abstract
- Protease-activated receptor-2 (PAR-2) plays a role in inflammatory reactions in airway physiology. Proteases cleaving the extracellular NH(2) terminus of receptors activate or inactivate PAR, thus possessing a therapeutic potential. Using RT-PCR and immunocytochemistry, we show PAR-2 in human airway epithelial cell lines human bronchial epithelial (HBE) and A549. Functional expression of PAR-2 was confirmed by Ca(2+) imaging studies using the receptor agonist protease trypsin. The effect was abolished by soybean trypsin inhibitor and mimicked by the specific PAR-2 peptide agonist SLIGKV. Amplitude and duration of PAR-2-elicited Ca(2+) response in HBE and A549 cells depend on concentration and time of agonist superfusion. The response is partially pertussis toxin (PTX) insensitive, abolished by the phospholipase C inhibitor U-73122, and diminished by the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Cathepsin G altered neither the resting Ca(2+) level nor PAR-2-elicited Ca(2+) response. Thermolysin, a prototypic bacterial metalloprotease, induced a dose-dependent Ca(2+) response in HBE, but not A549, cells. In both cell lines, thermolysin abolished the response to a subsequent trypsin challenge but not to SLIGKV. Thus different epithelial cell types express different PAR-2 with identical responses to physiological stimuli (trypsin, SLIGKV) but different sensitivity to modifying proteases, such as thermolysin.
- Subjects :
- Bronchi cytology
Bronchi drug effects
Calcium metabolism
Calcium Channels
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Humans
Immunohistochemistry
Inositol 1,4,5-Trisphosphate Receptors
Oligopeptides pharmacology
Pertussis Toxin
Receptor, PAR-2
Receptors, Cytoplasmic and Nuclear antagonists & inhibitors
Receptors, Thrombin drug effects
Respiratory Mucosa cytology
Respiratory Mucosa drug effects
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction drug effects
Signal Transduction physiology
Thermolysin pharmacology
Trypsin metabolism
Trypsin Inhibitors pharmacology
Virulence Factors, Bordetella pharmacology
Bronchi metabolism
Receptors, Thrombin metabolism
Respiratory Mucosa metabolism
Thermolysin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 282
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12003791
- Full Text :
- https://doi.org/10.1152/ajplung.00392.2001