The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation

Di, Anke; Gao, Xiao Pei; Qian, Feng; Kawamura, Takeshi; Han, Jin; Hecquet, Claudie; Ye, Richard D.; Vogel, Stephen M.; Malik, Asrar B.

doi:10.1038/ni.2171

Cited by 204 publications

(178 citation statements)

References 51 publications

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“…Redox signals are also known to affect Ca 2+ release from Ca 2+ stores (37), suggesting that ROS can regulate Ca 2+ signals in various ways. TRPM2 could play a part in this regulatory system, as suggested by a recent report demonstrating negative regulation of ROS by TRPM2 (9). Our findings suggest that the study of TRPM2 sensitization might identify unique approaches for determining the physiological function of TRPM2 that focus on body temperature and redox signals.…”

Section: °C (Student T Test)mentioning

confidence: 65%

“…Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca 2+ -permeable cation channel expressed by a wide range of immunocytes, including macrophages, whose function is gradually being clarified (3)(4)(5)(6)(7)(8)(9). We previously reported that heat stimulation activates TRPM2 in the presence of low concentrations of agonists, such as adenosine diphosphate ribose (ADPR) and related molecules (10).…”

Section: Calcium | Immune Cellsmentioning

confidence: 99%

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Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions

Kashio

Sokabe²,

Shintaku³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

158

117

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The ability to sense temperature is essential for organism survival and efficient metabolism. Body temperatures profoundly affect many physiological functions, including immunity. Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca 2+ -permeable cation channel expressed in a wide range of immunocytes. TRPM2 is activated by adenosine diphosphate ribose and hydrogen peroxide (H 2 O 2 ), although the activation mechanism by H 2 O 2 is not well understood. Here we report a unique activation mechanism in which H 2 O 2 lowers the temperature threshold for TRPM2 activation, termed “sensitization,” through Met oxidation and adenosine diphosphate ribose production. This sensitization is completely abolished by a single mutation at Met-214, indicating that the temperature threshold of TRPM2 activation is regulated by redox signals that enable channel activity at physiological body temperatures. Loss of TRPM2 attenuates zymosan-evoked macrophage functions, including cytokine release and fever-enhanced phagocytic activity. These findings suggest that redox signals sensitize TRPM2 downstream of NADPH oxidase activity and make TRPM2 active at physiological body temperature, leading to increased cytosolic Ca 2+ concentrations. Our results suggest that TRPM2 sensitization plays important roles in macrophage functions.

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Section: °C (Student T Test)mentioning

confidence: 65%

Section: Calcium | Immune Cellsmentioning

confidence: 99%

Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions

Kashio

Sokabe²,

Shintaku³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

158

117

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“…Macrophages, endothelial cells and neutrophils are crucial in regulating inflammation as well as lung vascular endothelial cell integrity in LPS-induced ALI (Di et al, 2012;Wang et al, 2011). We chose to study the macrophages because of their role in orchestrating inflammation (Kochanek et al, 2012;Song et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

Jayakumar

Samanta

Rajasingh

et al. 2015

Journal of Cell Science

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Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema, and respiratory failure. Here, we examined the efficacy of DNA methyl transferase (DNMT) inhibitor Aza (5-Aza 2-deoxycytidine), histone deacetylase (HDAC) inhibitor TSA (Trichostatin A), and combination therapy (Aza+TSA) in protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed a substantial attenuation of adverse lung histopathological changes, and inflammations. Importantly, these protective effects were due to significant macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK-HuR-TNF and activation of STAT3-Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI. This finding gives further evidence that the epigenetic treatment has a therapeutic potential for patients with sepsis.

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“…These cytokines and chemokines may induce circulating neutrophils to adhere to endothelial cells and migrate to tissues [16] . Depending on neutrophil activation, increased ROS and inflammatory products mediated by respiratory bursts may cause more oxidative damage [17,18] . Previously, it has been reported that oxidative stress and its damage mechanisms may cause infertility and early menopause [19] .…”

Section: Introductionmentioning

confidence: 99%

Sıçan Ovaryumlarında İskemi/Reperfüzyon Hasarı Üzerine Osajin’in Koruyucu Etkileri: Biyokimyasal ve Histopatolojik Değerlendirme

Çığşar¹,

Keleş²,

Can³

et al. 2015

Kafkas Univ Vet Fak Derg

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Reactive oxygen species (ROS) and inflammation play important roles in the pathogenesis of ischemia/reperfusion (I/R) ovarian injury. The purpose of this in-vivo study is to evaluate the effect of osajin, a prenylated flavonoid with antioxidant and anti-inflammatory properties, on oxidative balance and ovarian damage induced by unilateral I/R. The study used 48 adult, female Wistar albino rats. In the controls (CN), only laparotomy was performed. In group CN Osajin , 200 mg/kg osajin was administered. In group IR VEHICLE , an ischemic period of 3 h was followed by reperfusion for 3 h; the bilateral ovaries were then removed. In groups IR Osajin100 and IR Osajin200, after 3 h of ischemia, 100 and 200 mg/kg of osajin was given orally before reperfusion, respectively; after 3 h of reperfusion, the ovaries were removed. After the experiments, MPO, SOD and CAT enzyme activities and LPO levels was determined for the oxidative state and activities of PMNs. In addition, histopathological changes were examined in all rat ovarian tissues. Statistical analysis was performed using one-way ANOVA (with Duncan). According to biochemical and histopathological results, I/R increased LPO levels and MPO activities and infiltration of PMNs despite high-antioxidant SOD and CAT enzyme activity. Both dosage levels of osajin before I/R significantly decreased LPO level and MPO activity and PMN infiltration compared to those of the IR VEHICLE group, with the higher dosage causing greater decreases. In addition, results showed that treatment with osajin against ameliorated development of irreversible ovarian damage induced by I/R. These results suggest that osajin provides protections against ovarian I/R injury. Its mechanisms could be related to mitigation of oxidative stress and activities and to PMN infiltration. Osajin grubunda, sadece 200 mg/kg dozda osajin verildi. IR VEHICLE grubunda, 3 saatlik iskemik periyodu 3 saatlik reperfüzyon takip etti; daha sonra bilateral yumurtalıklar alındı. IR Osajin100 ve IR Osajin200 gruplarında 3 saatlik iskemiden sonra sırasıyla 100 ve 200 mg/kg osajin reperfüzyondan önce oral olarak verildi.; 3 saatlik reperfüzyondan sonra yumurtalıklar alındı. Deneylerden sonra, PMN'lerin aktiviteleri ve oksidatif durumları için MPO, SOD ve CAT enzim aktiviteleri ve LPO düzeyleri belirlendi. Ek olarak histopatolojik değişimler tüm rat ovaryum dokularında incelendi. İstatistiksel analizler one-way ANOVA kullanılarak yapıldı (Duncan ile). Biyokimyasal ve histopatolojik sonuçlara göre, yüksek antioksidan SOD ve CAT enzim aktivitesine rağmen, I/R PMN'lerin infiltrasyonunu, MPO aktivitelerini ve LPO düzeylerini artırdı. İskemik reperfüzyondan önce, osajinin her doz seviyesi büyük bir düşüşe sebep olan yüksek dozla birlikte IR VEHICLE grubunda olanlarla karşılaştırıldığında LPO düzeyi, MPO aktivitesi ve PMN infiltrasyonunu önemli derecede düşürdü. Ek olarak sonuçlar dönüşümsüz ovaryum hasarının iyileştirmeden gelişmesine karşın osajin ile tedavi I/R tarafından uyarılmış olduğunu gösterdi. Bu sonuçlar osajinin ...

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The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation

Cited by 204 publications

References 51 publications

Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions

Redox signal-mediated sensitization of transient receptor potential melastatin 2 (TRPM2) to temperature affects macrophage functions

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

Sıçan Ovaryumlarında İskemi/Reperfüzyon Hasarı Üzerine Osajin’in Koruyucu Etkileri: Biyokimyasal ve Histopatolojik Değerlendirme

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