Overexpression of ATP-Activated P2X7 Receptors on Immune and Non-Immune Cells of the Intestinal Mucosa is Implicated in the Pathogenesis of Crohn's Disease

Neves, Adriane R.; Yoshimoto, Agnes N.; Bernardazzi, Cláudio; Buongusto, Fernanda; Moraes, Luiza; Rosário, Alyson do; Martinusso, Cesonia A.; Elia, Celeste C.; Carneiro, Antonio José V.; Coutinho‐Silva, Robson; Castelo-Branco, Morgana T.; Souza, Heitor

doi:10.1016/s0016-5085(11)61957-4

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“…P2X7 is mainly expressed in cell types involving innate and adaptive immunity and is highly correlated with inflammation and immunity. It participates in inflammatory and nociceptive reactions of the organism to various pathological events (Chen et al, 2018 ; Neves et al, 2011 ; Souza et al, 2017 ). As demonstrated in Figure 4a , the expression of P2X7 was upregulated after acrylamide treatment.…”

Section: Resultsmentioning

confidence: 99%

“…However, the effect of acrylamide on the programmed death of immune cells such as macrophages, and its specific mechanism are still unclear. P2X7 (purinergic receptor P2X7) expressed in a variety of immune cells plays an important role in regulating immune response (Neves et al, 2011). P2X7 becomes activated when pathological conditions like hypoxia or cell destruction occur (Markwardt, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…P2X7 (purinergic receptor P2X7) expressed in a variety of immune cells plays an important role in regulating immune response (Neves et al, 2011 ). P2X7 becomes activated when pathological conditions like hypoxia or cell destruction occur (Markwardt, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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The inhibitory effect of Yam polysaccharides on acrylamide‐induced programmed cell death in RAW 264.7 cells

Wang

Han

Wang

et al. 2022

Food Science & Nutrition

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Acrylamide has been well known for its neurotoxicity, genotoxicity, carcinogenicity, etc. Recently, the immunotoxicity of acrylamide has been reported by different research groups, although the underlying mechanisms of acrylamide endangering immune systems have not been fully elucidated. In this study, mouse monocyte–macrophage cells model was used to clarify the toxic mechanism of acrylamide and the inhibitory effect of Yam polysaccharides (YPS) on acrylamide‐induced damage. We found that acrylamide induced RAW 264.7 cell death in a time‐ and concentration‐dependent manner. After acrylamide (2.0, 3.0, 4.0 mmol/L) treatment for 24 h, cell apoptosis, autophagy, and pyroptosis were observed. However, the levels of autophagy and pyroptosis decreased at a high concentration of acrylamide (4.0 mmol/L). Acrylamide upregulated P2X7 expression, but the P2X7 level was not showing a monotone increasing trend. When the P2X7 antagonist was applied, the effect of acrylamide on autophagy and pyroptosis was weakened. Additionally, acrylamide triggered the occurrence of oxidative stress and a decreased nitric oxide (NO) level. However, reactive oxygen species (ROS) generation, the decrease of heme oxygenase‐1 (HO‐1) expression, and the increase of inducible nitric oxide synthase (iNOS) expression were reversed by the inhibition of P2X7. Yam polysaccharides (50.0 μg/ml) significantly inhibited acrylamide‐induced oxidative stress and cell death (including apoptosis, autophagy, and pyroptosis). Yam polysaccharides also effectively reversed the increase of iNOS expression induced by acrylamide. However, Yam polysaccharides promoted the expression of P2X7 rather than prohibit it. These results indicated that acrylamide caused RAW 264.7 cell death due to pro‐apoptosis as well as excessive autophagy and pyroptosis. Apoptosis might be more predominant than autophagy and pyroptosis under a higher concentration of acrylamide (4.0 mmol/L). P2X7‐stimulated oxidative stress was responsible for acrylamide‐induced programmed cell death (PCD), but P2X7 showed limited regulatory effect on apoptosis. Yam polysaccharides with antioxidant activity inhibited acrylamide‐induced cell death (apoptosis, autophagy, and pyroptosis), but exerted limited effect on the acrylamide‐induced P2X7 expression. These findings would offer an insight into elucidating the immunotoxic mechanism of acrylamide and the potential approaches to control its toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%