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Celastrol attenuates fMLP-induced superoxide anion generation, myeloperoxidase production, and elastase release by human neutrophils


Nipapan Malisorn
Ammara Chaikan

Abstract

Purpose: To investigate the anti-inflammatory effect of celastrol via attenuation of formyl-methionylleucyl-phenylalanine (fMLP)-induced superoxide generation, myeloperoxidase production, and elastase release by peripheral blood neutrophils.


Methods: Cytotoxicity of celastrol on human peripheral blood neutrophils was investigated using a 2Htetrazolium hydroxide (XTT) assay. Human neutrophils were stimulated with 100-nM fMLP; the effect of celastrol on superoxide generation was determined via ferricytochrome C reduction, the effect on myeloperoxidase production by tetramethylbenzidine oxidation, and the effect on elastase activity by Boc-Ala-ONp hydrolysis.


Results: Treatment of human neutrophils with celastrol showed dose-dependent inhibition of fMLPinduced superoxide generation, myeloperoxidase production, and elastase release with half-maximal inhibitory concentration (IC50) values of 5.9 ± 0.1, 1.9 ± 0.2, and 1.5 ± 0.1 µM, respectively.


Conclusion: These results indicate that celastrol possesses anti-inflammatory properties via attenuation of fMLP-induced superoxide generation, myeloperoxidase production, and elastase release by peripheral blood neutrophils.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996