Emodin inhibits ATP-induced IL-1β secretion, ROS production and phagocytosis attenuation in rat peritoneal macrophages via antagonizing P2X₇receptor

Abstract

Emodin inhibits ATP-induced IL-1β secretion, ROS production and phagocytosis attenuation in rat peritoneal macrophages via antagonizing P2X 7 receptor, Pharmaceutical Biology, 52:1, 51-57, DOI: 10.3109/13880209.2013 ] c increase evoked by ATP (5 mM) was inhibited by emodin, in a dose-dependent manner with IC 50 of 0.5 mM. Furthermore, emodin reduced the IL-1b release induced by ATP (2 mM) in lipopolysaccharide (LPS)-activated macrophages, with an IC 50 of 1.6 mM. Emodin also strongly suppressed the ROS production and phagocytosis attenuation triggered by ATP (1 mM), with IC 50 values of 1 mM and 0.7 mM, respectively. Besides, BBG, a specific antagonist of P2X 7 R, exhibited similar suppressive effects on these inflammation responses. Conclusion: These results showed the inhibitory effects of emodin on ATP-induced [Ca 2+ ] c increase, IL-1b release, ROS production and phagocytosis attenuation in rat peritoneal macrophages, by inhibiting the activation of P2X 7 R.

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

“…The study suggested that-via ROS production-P2X7Rs play a critical role in macrophage inflammatory and antimicrobial activities [217]. Similarly, rat peritoneal macrophages were found to respond to ATP with ROS production, presumably involving P2X7Rs [218]. Also, stimulation of the NR8383 rat alveolar macrophage cell line with ATP (mostly via P2X7Rs) and other extracellular nucleotides lead to transient production of high levels of ROS.…”

“…They function as widespread signal Prostacyclin release from endothelial cells [195][196][197][198] Thromboxane A2 (TXA2) ATP, ADP/P2Y 12 TXA2 release from platelets, astrocytes [199][200][201] Thromboxane B2 (TXB2) ATP/P2X7 TXB2 release from primary human peritoneal macrophages and blood monocytes [202] Leukotriene B4 (LTP4) ATP/P2X7 LTP4 release from primary human peritoneal macrophages and blood monocytes [202] Sphingosine 1-phosphate ATP via ABCA family transporter Sphingosine 1-phosphate release from rat platelets [203] Nitric ROS release from numerous cell types [217][218][219][220] substances activating P2XRs and P2YRs [221]. In peripheral synapses, ATP can act as fast neurotransmitter through its own postsynaptic P2XRs.…”

Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection

“…Activation of P2X7 receptors by extracellular ATP plays a central role in the induction of inflammation (12–14). For example, it triggers the release of proinflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, and IL-18 (14, 15) and prompts activation of NLPR3 inflammasome (12, 16, 17), production of reactive oxygen species (18–20), and induction of apoptosis (21, 22). …”

The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease

“…In addition to the nonspecific and specific P2X7 antagonists listed above, a number of other compounds have been shown to block P2X7 activation, many with IC 50 values in the micromolar range (Table 3). Naturally derived compounds such as the traditional Chinese herb emodin Jelassi et al, 2013;Zhu et al, 2014), the plant-derived alkaloids berberine and sanguinine , niphatoxin C, sytlissadine A and sytlissadine B from the marine sponge (Buchanan et al, 2007a,b), and the estrogen hormone 17b-estradiol (CarioToumaniantz et al, 1998) [N- [2-(4-oxo-1-phenyl-1, 3, 8-triazaspiro[4, 5]dec-8-yl) ethyl]-2-naphthalenecarboxamide], and halopemide) (Pupovac et al, 2013b) can each directly block P2X7. In this regard, studies investigating signaling pathways downstream of P2X7 activation through the use of enzyme inhibitors need to ensure that such compounds do not directly impair P2X7.…”