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Inhibition of neutrophil functions by chalcone derivative via a cAMP‐dependent pathway
Author(s) -
Hwang TsongLong,
Leu YannLii,
Yeh ShangHsin
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1144-c
Subject(s) - chemistry , superoxide , chalcone , biochemistry , phosphodiesterase , adenosine , pharmacology , biology , enzyme , stereochemistry
Chalcone is abundantly present in the plant kingdom and has various biological activities such as anti‐inflammatory and antioxidant. In this study, the semisynthetic chalcone derivative, 3¡¦‐isopropoxychalcone (H2O7D), was demonstrated to inhibit the generation of superoxide and the release of elastase, as well as to accelerate resequestration of cytosolic calcium in formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine‐activated human neutrophils. The inhibitory effects of H2O7D were reversed by protein kinase (PK)A inhibitors, as well as adenosine deaminase (ADA) and a selective A2a‐receptor antagonist. In contrast, H2O7D displayed no antioxidant or superoxide‐scavenging ability, and it failed to alter the subcellular NADPH oxidase activity. H2O7D induced a substantial increase in cAMP but not cGMP levels. The elevation of cAMP formation by H2O7D was inhibited by ADA. These results show that cAMP mediates the H2O7D‐caused inhibition of human neutrophils. Furthermore, H2O7D inhibited phosphodiesterase (PDE) activities, but it did not alter AC and sGC activities. In summary, these results indicate that the inhibitory effect of H2O7D is cAMP/PKA‐dependent, and that it occurs through inhibition of cAMP PDE, which potentates the autocrine functions of endogenous adenosine. Inhibition of respiratory burst and degranulation in human neutrophils may give this drug the potential to protect against the progression of inflammation.