Capsaicin inhibits platelet-activating factor-induced cytosolic Ca2+ rise and superoxide production.
Platelet-activating factor (PAF) is an important participant in the inflammatory process. We studied the regulation of PAF activity by capsaicin in human promyelocytic leukemia HL-60 cells. Capsaicin inhibited PAF-induced superoxide production in a concentration-dependent manner. In addition to PAF, the fMLP- and extracellular ATP-induced superoxide productions were inhibited by capsaicin, whereas PMA-induced superoxide production was not affected. In the PAF-stimulated cytosolic Ca2+ increase, capsaicin inhibited in particular the sustained portion of the raised Ca2+ level without attenuation of the peak height. In the absence of extracellular Ca2+, the PAF-induced Ca2+ elevation was not inhibited by capsaicin because capsaicin only inhibited the Ca2+ influx from the extracellular space. In addition, capsaicin did not affect PAF-induced inositol 1,4,5-trisphosphate production, suggesting that phospholipase C activation by PAF is not affected by capsaicin. Store-operated Ca2+ entry (SOCE) induced by thapsigargin was inhibited by capsaicin in a concentration-dependent manner. This capsaicin effect was also observed on thapsigargin-induced Ba2+ and Mn2+ influx. Furthermore, capsaicin's inhibitory effect on the thapsigargin-induced Ca2+ rise overlapped with that of SK&F96365, an inhibitor of SOCE. Both capsaicin and SK&F96365 also inhibited PAF-induced cytosolic superoxide generation in HL-60 cells differentiated by all-trans-retinoic acid. Our data suggest that capsaicin exerts its anti-inflammatory effect by inhibiting SOCE elicited via PLC activation, which occurs upon PAF activation and results in the subsequent superoxide production.
Choi
S Y
SY
Department of Life Science, Pohang University of Science and Technology, Republic of Korea.
Ha
H
H
Kim
K T
KT
D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002211:Capsaicin / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019284:Thapsigargin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D013481:Superoxides; D019284:Thapsigargin; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002211:Capsaicin; D002118:Calcium