Inhibition of ATP-induced macrophage death by emodin via antagonizing P2X7 receptor.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone), an anthraquinone derivative from Rheum officinale Baill, exhibits anti-inflammatory and immunosuppressive activities, however, the underlying mechanisms are not fully understood. This study examined the effects of emodin on ATP-evoked responses in rat peritoneal macrophages and in human embryonic kidney 293 cells (HEK293) heterologously expressing the cloned rat P2X7 receptor. Emodin reduced macrophage death induced by millimolar ATP in a concentration-dependent manner with the half of maximal inhibition values (IC50) of 0.2 microM. It also strongly inhibited ATP-induced dye uptake or pore formation, a hallmark property associated with P2X7 receptor activation, and 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP) induced increases in intracellular Ca2+ concentrations in macrophages with an IC50 of 0.5 microM. Furthermore, emodin significantly suppressed BzATP-evoked currents in P2X7 receptor expressing HEK293 cells with an IC50 of 3.4 microM. Taken together, these results provide compelling evidence for a novel action of emodin as a P2X7 receptor antagonist, which may underlie its anti-inflammatory and immunosuppressive activities.
Liu
Lijun
L
Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin, 300071, PR China.
Zou
Jie
J
Liu
Xing
X
Jiang
Lin-Hua
LH
Li
Junying
J
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004553:Electric Conductivity; D004642:Emodin / Q000494:pharmacology*; D004996:Ethidium / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D004996:Ethidium; D004642:Emodin; D002118:Calcium