Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats

Guan, Xue-Hai; Fu, Qiaochu; Shi, Dai; Bu, Huilian; Song, Zhenpeng; Xiong, Bingrui; Shu, Bin; Xiang, Hong‐Bing; Xu, Bing; Manyande, Anne; Cao, Fei; Tian, Yuan

doi:10.1016/j.expneurol.2014.09.019

Cited by 84 publications

(84 citation statements)

References 102 publications

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“…In vivo immunofluorescence staining has also shown that CXCR3 co-localizes with spinal microglia and astrocytes in a rat model of bone cancer-induced pain [11,14]. The neutralization of CXCR3 significantly reduces the expression of markers of activated microglia and astrocytes as well as the levels of proinflammatory cytokines and chemokines, such as CCL2 and CXCL10 [11,12,14]. Thus, microglia and astrocytes participate in the development of inflammatory pain and act as the targets of the chemokine-receptor pair CXCL10/CXCR3.…”

Section: Introductionmentioning

confidence: 99%

“…CXCL10 is expressed at low levels in the spinal cord under normal conditions, but upon stimulation, the expression of this chemokine is substantially increased at sites where glial cells accumulate [11]. In vivo immunofluorescence staining has also shown that CXCR3 co-localizes with spinal microglia and astrocytes in a rat model of bone cancer-induced pain [11,14]. The neutralization of CXCR3 significantly reduces the expression of markers of activated microglia and astrocytes as well as the levels of proinflammatory cytokines and chemokines, such as CCL2 and CXCL10 [11,12,14].…”

Section: Introductionmentioning

confidence: 99%

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Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion

Qian¹,

Tian²,

Tian³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Spinal microglia and astrocytes are the main responders to the inflammatory cascade and process pain through various neural interactions. CXCL10 is a late-phase protein that accelerates arteriogenesis during reperfusion through CXCR3. However, the early-phase expression (within 72 h postoperatively) of CXCL10 and CXCR3 during the development of ischemia-reperfusion (IR)-induced inflammatory pain remains unclear. We investigated whether this chemokine pair participates in glial interactions during early-phase IR injury. Methods: A rat model was induced by an 8-min occlusion of the aortic arch. Temporal assessments of mechanical and thermal allodynia and the protein levels of CXCL10 and CXCR3 were determined through measurements of paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) and Western blotting assays. The co-localization of various cells with glial cells was detected by double immunofluorescence. The effects of CXCL10/CXCR3 on glial interactions were explored by intrathecal treatment with specific inhibitors (AMD487, minocycline and fluorocitrate) and recombinant CXCL10, and subsequent release of cytokines was assessed by ELISAs. Results: The IR injury initiated bimodal allodynia within 72 h of reperfusion, as illustrated by two W-shape trends in the PWTs and PWLs with two minima at 12 and 48 h post-IR. Allodynia was highly correlated with overexpression of CXCL10 and CXCR3, which were expressed in microglia at the early stage and in both microglia and astrocytes at the late stage, as shown by increased CXCL10 and CXCR3 immunoreactivities and double-labeled cells. AMD487 and minocycline injections exerted comparable inhibitory effects on CXCR3 and Iba-1 and on GFAP immunoreactivity at 12 and 48 h post-IR, and these inhibitory effects were only observed at 48 h following fluorocitrate injection. The levels of TNF-α and IL-6 showed variations in concert with the changes in Iba-1 and GFAP immunoreactivities. Recombinant CXCL10 injection reversed the abovementioned effects. Conclusion: The results showed that CXCL10/CXCR3 are involved in bimodal inflammatory pain during early-phase IR injury. The sequential activation of and crosstalk between microglia and astrocytes mediated through CXCR3 upregulation suggested that treatments targeting specific cell types are important in post-IR allodynia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion

Qian¹,

Tian²,

Tian³

et al. 2018

Cell Physiol Biochem

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“…Цитокин ИЛ-1β также участвует с другими цитокинами в генезе нейропатической боли [17]. CXCR3 имеет ключевое значение при развитии костной онкологической боли, действуя через внутриклеточный Akt-киназный и внеклеточный ERKкиназный сигнальные пути [18]. Известные на данный момент три варианта сплайсинга CXCR3 обеспечивают фенотипическую изменчивость болевого синдрома, что является предметом даль-нейшего изучения [18].…”

Section: аннотацияunclassified

Cytokine Gene Polymorphisms as Predictors of Chronic Pain Syndrome in Oncology

Боброва¹,

Shnayder²,

Петрова³

et al. 2017

Sib. onkol. ž.

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Высокая распространенность хронического болевого синдрома среди пациентов онкологиче-ского профиля, реализующегося под действием множества факторов, а также динамичный прирост фармакорезистентной боли у данной группы паци-ентов на современном этапе развития клинической онкологии предопределяют понимание сложных механизмов болевого синдрома, лежащих в основе формирования данной нозологической формы как необходимого условия эффективной и безопасной анальгетической терапии [1]. Известно, что по-вреждение периферических нейронов активирует каскад патофизиологических процессов, затраги-вающих центральную и периферическую ноцицеп-тивную систему, вызывая тем самым повышение болевой чувствительности [2]. У пациентов со злокачественными новообразованиями ноцицеп-тивные рецепторы возбуждаются в ответ на воз-действие воспалительных и продуцируемых самой опухолью альгогенов, усиливая выраженность DOI: 10.21294/1814DOI: 10.21294/ -4861-2017 Для цитирования: Боброва О.П., Шнайдер Н.А., Петрова М.М., Зырянов С.К., Сычев Д.А. Генетический полиморфизм цито-кинов как предиктор фенотипической реализации хронического болевого синдрома в онкологии. Сибирский онкологический журнал. 2017; 16 (5): 87-94. -DOI: 10.21294/181487-94. -DOI: 10.21294/ -4861-2017 For citation : Bobrova O.P., Shnayder N.A., Petrova M.M., Zyryanov K.S., Sychev D.A. Cytokine gene polymorphisms as predictors of chronic pain syndrome in oncology. Siberian Journal of Oncology. 2017; 16 (5): 87-94. -DOI: 10.21294/1814 16 (5): 87-94. -DOI: 10.21294/ -4861-2017 (1996-2016 гг.), поиск которых осущест-влялся по ключевым словам на русском (цитокин, фармакогенетика, однонуклеотидные полиморфиз-мы (ОНП), опухоль) и английском языках (cytokine, pharmacogenetics, singlenucleotidepolymorphisms (SNPs), tumor). Этот вид поиска по ключевым словам был оптимальным выбором.В обзор были включены исследования в упо-мянутых выше базах данных с полным текстом, а также описания в виде тезисов (abstract), учитывая язык оригинального текста. Все найденные публи-кации подробно изучались. В список для после-дующего анализа включались только те материалы, которые удовлетворяли критериям поиска.Локализация проанализированных нами ге-нов цитокинов (интерлейкинов) и их рецепторов представлена в табл. 1. Сводные данные изуче-ния одиночных нуклеотидных полиморфизмов (ОНП) генов, кодирующих известные цитокины и предопределяющих фенотипическую реализацию возникновения злокачественных новообразований (ЗНО), представлены в табл. 2.Современные исследования показывают, что цитокины могут обусловливать индивидуальные различия болевого синдрома в онкологии, что объясняется наличием известных ОНП генов, из- Носительство ОНП 174G>C (rs1800795) про-мотора гена IL-6 связано с изменениями сыворо-точного уровня одноименного цитокина ИЛ-6. У гомозиготных носителей генотипа GG уровень продуцирования ИЛ-6 выше в сравнении с гомо-зиготными носителями генотипа СС. Большинство афроамериканцев (83,6 %) и латиноамериканцев (70,5 %) являются носителями гомозиготного гено-типа GG, а европейцы в 45,5 % случаев являютс...

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“…2 μg of total RNA was extracted from the myocardial ischemic regions responding to I/R using TRIzol reagent (Invitrogen, USA) as described previously [43][44][45][46][47]. The threshold cycle (CT) was used to estimate the amount of target mRNA.…”

Section: Real-time Quantitative Pcrmentioning

confidence: 99%

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

Li¹,

Lin²,

He³

et al. 2018

Oncotarget

Self Cite

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We used Agilent Gene Expression microarray to analyze differential gene and lncRNA expression patterns in the myocardial ischemia regions during ischemia/ reperfusion (I/R)-induced cardiac injury in rats. Male SD rats were assigned into control group, 2 h group (30 min ischemia followed by 2 h reperfusion), 0.5 h (30 min ischemia followed by 0.5h reperfusion) group. We observed that of 18090 lncRNAs, an average of 233 lncRNAs was up-regulated in ischemic tissues of 2 h group, compared with those in control group, while an average of 6115 lncRNAs was down-regulated (with a > 2.0 fold-change and p < 0.05). Further, a total of 3135 mRNAs were differentially expressed between control group and 2h group, in which 542 mRNAs were up-regulated and 2593 mRNAs were down-regulated. Some differentially expressed genes were validated by qRT-PCR analyses of select lncRNAs in different time points after cardiac I/R injury. We unveiled that the expressions of lncRNA XR_345533.2, NONRATT025386, NONRATT024318, XR_599241.1, and NONRATT025509 were significantly up-regulated in 2h group compared with control group and 0.5h group, whereas the expression of lncRNA NR_130708.1 was downregulated after cardiac I/R injury and had no statistically different between 0.5h group and 2h group. Otherwise, the expressions of lncRNA NONRATT028627, NONRATT021959, XR_590005.1 and NONRATT023191 were significantly up-regulated in 2h group compared with 0.5h group. These findings provide evidence for differential expression patterns of mRNAs and lncRNAs in the ischemic tissues after cardiac I/R injury in rats.

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Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats

Cited by 84 publications

References 102 publications

Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion

Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion

Cytokine Gene Polymorphisms as Predictors of Chronic Pain Syndrome in Oncology

Altered myocardial gene expression profiling in the ischemic tissues at different time points after cardiac ischemia/reperfusion in rats

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