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Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin
Joachim J Ubl1, Zoryana V Grishina, Tatiana K Sukhomlin
1Institut für Neurobiochemie, 39120 Magdeburg, Germany.
Summary
Protease-activated receptor-2 (PAR-2) is present in human airway cells and mediates inflammatory responses. Different airway cell types exhibit distinct sensitivities to proteases that activate PAR-2, suggesting targeted therapeutic potential.
Area of Science:
- Cellular and Molecular Biology
- Respiratory Physiology
- Pharmacology
Background:
- Protease-activated receptor-2 (PAR-2) is implicated in airway inflammation.
- Proteases activating PAR-2 offer therapeutic possibilities by modulating receptor activity.
Purpose of the Study:
- To investigate the presence and function of PAR-2 in human airway epithelial cells.
- To characterize the signaling pathways involved in PAR-2 activation.
- To examine the differential effects of various proteases on PAR-2 in distinct cell types.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry to detect PAR-2.
- Calcium (Ca2+) imaging studies using protease agonists (trypsin, SLIGKV) and inhibitors.
- Assessment of signaling pathway involvement using pertussis toxin, U-73122, and 2-aminoethoxydiphenyl borate.
Main Results:
- PAR-2 was detected in human bronchial epithelial (HBE) and A549 cell lines.
- Trypsin and the peptide agonist SLIGKV elicited dose- and time-dependent Ca2+ responses, partially PTX-insensitive and dependent on phospholipase C and IP3.
- Thermolysin induced Ca2+ responses in HBE cells but not A549 cells, and it desensitized subsequent trypsin activation, but not SLIGKV activation.
Conclusions:
- Human airway epithelial cells express functional PAR-2.
- PAR-2 activation involves complex signaling pathways sensitive to different proteases.
- Differential protease sensitivity of PAR-2 in various airway epithelial cells highlights cell-specific responses and therapeutic potential.