PAR-2 activation, PGE2, and COX-2 in human asthmatic and nonasthmatic airway smooth muscle cells.
The protease-activated receptor-2 (PAR-2) is present on human airway smooth muscle (ASM) cells and can be activated by mast cell tryptase, trypsin, or an activating peptide (AP). Trypsin induced significant increases in PGE2 release from human ASM cells after 6 and 24 h and also induced cyclooxygenase (COX)-2 mRNA expression and COX-2 protein. Tryptase and the PAR-2 AP did not alter PGE2 release or COX-2 protein levels, suggesting a lack of PAR-2 involvement. When we compared results in asthmatic and nonasthmatic muscle cells, both trypsin and bradykinin induced less PGE2 from asthmatic ASM cells, and bradykinin induced significantly less COX-2 mRNA in asthmatic cells. Significantly less PGE2 was released from proliferating ASM cells from asthmatic patients. In conclusion, trypsin induces PGE2 release and COX-2 in human ASM cells, which is unlikely to be via PAR-2 activation. In addition, ASM cells from asthmatic patients produce significantly less PGE2 and COX-2 compared with nonasthmatic cells. These findings may contribute to the increase in muscle mass evident in asthmatic airways.
Chambers
Linda S
LS
Dept. of Pharmacology, Univ. of Sydney, New South Wales 2006, Australia.
Black
Judith L
JL
Ge
Qi
Q
Carlin
Stephen M
SM
Au
Wendy W
WW
Poniris
Maree
M
Thompson
Joanne
J
Johnson
Peter R
PR
Burgess
Janette K
JK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D053802:Tryptases
D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D012697:Serine Endopeptidases; D014357:Trypsin; D053802:Tryptases; D015232:Dinoprostone; D001920:Bradykinin