Reactive oxygen species mediate chloroquine‐induced expression of chemokines by human astroglial cells

Park, Jinseu; Choi, Kyunghee; Jeong, Eun-Joo; Kwon, Daeho; Benveniste, Etty N.; Choi, Chulhee

doi:10.1002/glia.20017

Cited by 74 publications

(70 citation statements)

References 52 publications

(80 reference statements)

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“…The role of ROS in NF-jB activation has been studied using a variety of techniques, e.g. a murine model for CGD [15], or cells in the presence of various antioxidants/NADPH-oxidase inhibitors [12,13,19,35]. These reports suggest that a lack of ROS production leads to diminished NF-jB activation and thus decreased inflammatory responses, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Most of these studies have employed various antioxidants or NADPH-oxidase inhibitors to abrogate ROS; in the presence of these agents NF-jB activation was blocked [16][17][18] and cytokine production diminished [12,19,20]. In the presence of diphenyleneiodonium (DPI; a NADPH-oxidase inhibitor), a marked decrease in TNF-a production after stimulation was recorded (Fig.…”

Section: Cgd Leukocytes Produce Increased Amounts Of Proinflammatory mentioning

confidence: 99%

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Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS‐independent activation of NF‐κB

et al. 2007

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Reactive oxygen species (ROS) generated by the cellular NADPH-oxidase are crucial for phagocytic killing of ingested microbes and have been implicated as signaling molecules in various processes. For example, ROS are thought to be involved in activation of the transcription factor NF-jB, central for mediating production of proinflammatory cytokines in response to inflammatory stimuli. Several studies have demonstrated that inhibitors of the NADPH-oxidase interfere with NF-jB activation and production of proinflammatory cytokines. Curiously, patients with chronic granulomatous disease (CGD), an immunodeficiency characterized by an inability to produce ROS, are not only predisposed to severe infections, but also frequently develop various inflammatory complications indicative of exaggerated inflammatory responses. Here, we show that human CGD leukocytes display a hyperinflammatory phenotype with increased production of proinflammatory cytokines in response to stimulation with Toll-like receptor agonists. The hyperinflammatory phenotype was also evident in mononuclear cells from CGD mice (gp91 phox-/-), but not in control cells in the presence of NADPHoxidase inhibitor diphenyleneiodonium, probably reflecting NADPH-oxidase-independent effects of the inhibitor. Furthermore, we show that the major steps involved in NFjB activation were intact in human CGD cells. These data indicate that ROS were nonessential for activation of NF-jB and their production may even attenuate inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Cgd Leukocytes Produce Increased Amounts Of Proinflammatory mentioning

confidence: 99%

Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS‐independent activation of NF‐κB

et al. 2007

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“…This is because expression of pro-inflammatory cytokines, such as TNF-α and IL-1β, but not IL-6, in human astroglial cells depends on the activation of nuclear factor (NF)-kappaB by ROS generation. 15 Another study is needed to determine whether a cause-andeffect relationship exists between O 2 -production activity of neutrophils and cytokine production in preterm infants with early PVL.…”

Section: Discussionmentioning

confidence: 99%

Increased inflammatory markers are associated with early periventricular leukomalacia

Tsukimori

Komatsu

Yoshimura

et al. 2007

Develop Med Child Neuro

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The aim of the study was to investigate whether inflammatory markers are associated with the occurrence of periventricular leukomalacia (PVL). Superoxide (O2‐) production of neutrophils and plasma antioxidative superoxide dismutase (SOD) activity in umbilical cord blood were studied. Participants were preterm infants with early PVL (n=6; three males, three females; mean birthweight 1458g [SD 517], range 620–2040g; mean gestational age 29.8wks [SD 2.9], range 27–34wks); and preterm control infants without PVL (n=10; five males, five females; mean birthweight 1838g [SD 664], range 925–2748g; mean gestational age 30.6wks [SD 3.1], range 26–34wks). In addition, pro‐inflammatory cytokine levels were measured in the umbilical cord blood. N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced O2‐ production by neutrophils in infants with early PVL was significantly higher than that in the control group. In contrast, there was no significant difference in concentrations of copper/zinc‐SOD and SOD activity between groups. Concentrations of interleukin (IL)‐1β and tumour necrosis factor‐α (but not IL‐6, IL‐8, or granulocyte‐colony stimulating factor) were significantly higher in infants with early PVL than in control infants. The excess O2‐ produced by activated neutrophils with increased pro‐inflammatory cytokine production could play a role in the molecular cascade leading to white matter damage in PVL.

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“…Можно пред-положить, что хлорохин, по-видимому, через механизм генерации ROS, в котором, как предполагается, задей-ствована NOX (и ее активация хлорохином), активирует NF-κB и последующую экспрессию широкого спектра интерферонов, цитокинов и хемокинов (Park et al, 2003(Park et al, , 2004.…”

Section: Discussionunclassified

Expression of genes of cytokines, transcription factors and differentiation antigens in human dendritic cells activated by double-stranded DNA

Proskurina¹,

Orishchenko²,

Potter³

et al. 2017

Vestn. VOGiS

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One of the most important properties of extracellular double-stranded DNA related to the treatment of various diseases is its ability to activate effector cells of the immune system (anti-tumor and vaccinal immunity) through dendritic cells (DCs). The stimulatory effect of DNA on DCs is mediated by the TLR9 signaling pathway and/or through a system of cytosolic sensors and is manifested by increased expression of MHC class II antigens and costimulatory molecules and by increased synthesis of immunoregulatory cytokines. In this work, the expression of cytokines, differentiation antigens and transcription factor genes has been investigated in DCs activated by double-stranded human DNA (i) without any additional factors, (ii) using a lipophilic agent, and (iii) by blocking TLR9 with chloroquine. Evaluation of the DNA effect was carried out after the 6-and 24-hour exposure. It was found that the preparation of double-stranded DNA transfected by Lipofectamine 2000 boosts DCs at the same level as Poly(dA : dT), a synthetic equivalent of double-stranded DNA. It was discovered that combined application of DNA and chloroquine enhances expression of the IFN-α, IL8, МСР1, VEGF, CD25, and CD83 genes by hour 24 of incubation. It was for the first time shown that genomic "self" double-stranded DNA as a mono agent activates mRNA synthesis of cytokines IFN-α, IFN-β, IFN-γ, IL8, IL10, and VEGF in DCs at 6 hours of induction.Key words: chloroquine; double-stranded DNA; cytokines; dendritic cells; real-time PCR.Одно из важнейших свойств экстраклеточной двуцепочечной ДНК, имеющее отношение к терапии различных заболеваний, -это ее способность через дендритные клетки (ДК) активировать эффекторные клетки иммунной системы (противоопухолевый и вакцинальный иммунитет). Стимулирующий эффект ДНК на ДК опосредуется через TLR9 сигнальный путь и/или через систему цитозольных сенсоров и проявляется усилением экспрессии МНС антигенов II класса и костимулирующих молекул, а также синтеза иммунорегуляторных цитокинов. В настоящей работе была иссле-дована экспрессия генов цитокинов, антигенов дифференцировки и факторов транскрипции в ДК, активированных двуцепочечной ДНК человека: (1) без использования каких-либо дополнительных факторов, (2) при использовании липофильного агента и (3) при блокировании TLR9 хлорохином. Оценка эффекта ДНК проводи-лась после 6-и 24-часовой экспозиции. Показано, что препарат двуцепочечной ДНК при трансфекции липофектамином активиру-ет ДК на таком же уровне, как и Poly(dA : dT), синтетический аналог двуцепочечной ДНК. Установлено, что совместная обработка ДНК и хлорохином усиливает экспрессию генов ИФН-α, ИФН-β, ИФН-γ, ИЛ8, МСР1, VEGF, CD25 и CD83 к 24 ч инкубации. Впервые показано, что геномная «self» двуцепочечная ДНК как монопрепарат акти-вирует синтез мРНК ИФН-α, ИФН-β, ИФН-γ, ИЛ8, ИЛ10 и VEGF в ДК к 6 часам индукции.

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Reactive oxygen species mediate chloroquine‐induced expression of chemokines by human astroglial cells

Cited by 74 publications

References 52 publications

Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS‐independent activation of NF‐κB

Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS‐independent activation of NF‐κB

Increased inflammatory markers are associated with early periventricular leukomalacia

Expression of genes of cytokines, transcription factors and differentiation antigens in human dendritic cells activated by double-stranded DNA

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