右美托咪定复合依托咪酯对老年大鼠肝部分切除诱导术后认知功能障碍的改善作用

目的探究右美托咪定复合依托咪酯对全麻老年大鼠肝部分切除术后认知功能障碍的改善作用。方法雄性大鼠随机分为对照组、模型组、右美托咪定组、依托咪酯组、右美托咪定复合依托咪酯组,每组12只。2%异氟烷麻醉后,行气管插管机械通气,持续吸入1.5%异氟烷。右美托咪定组麻醉诱导给予6μg/kg右美托咪定10 min静注完毕,依托咪酯组麻醉诱导给予1.20 mg/kg依托咪酯静注,依托咪酯复合右美托咪定组麻醉诱导静注1.20 mg/kg依托咪酯和6μg/kg右美托咪定(10min静注完毕),模型组全麻气管插管不给予任何静脉麻醉药物,对照组不给予任何处理。实验组和模型组分别在全麻气管插管药物诱导后行肝部分切除术,造术后认知功能障碍的模型,对照组不予任何处理。术前1 d、术后1~5 d进行Morris水迷宫实验,术后第6天进行空间探索测试记忆能力。取术前1 d、术后1、3、5 d大鼠尾静脉血样,采用酶联免疫测定IL-6水平。结果与模型组比较,右美托咪定组、依托咪酯组、依托咪酯复合右美托咪定组的潜伏期显著缩短(P0.05);与模型组比较,右美托咪定组、依托咪酯复合右美托咪定组穿越平台次数显著增加(P0.01),目标象限停留时间比显著增加(P0.01),IL-6水平显著降低(P0.05)。结论右美托咪定复合依托咪酯可降低老年大鼠肝部分切除术后炎症因子水平,改善其术后认知功能。     

PI3K/Akt/HIF-1α信号通路在右美托咪定减轻大鼠肺缺血再灌注损伤中的作用

目的：评价磷脂酰肌醇3-激酶-丝氨酸-苏氨酸蛋白激酶-缺氧诱导因子-1α（phosphatidylinositol 3-kinase-protein-serine-threonine kinases-hypoxia inducible factor-1α,PI3K-Akt-HIF-1α）信号通路在右美托咪定减轻大鼠肺缺血再灌注损伤中的作用。方法：清洁级健康成年雄性SD大鼠32只,体质量250~350 g,采用随机数字表法分为4组（n=8）：假手术组（Sham组）、缺血再灌注组（IR组）、IR+右美托咪定组（D组）、IR+右美托咪定+LY294002组（DL组）。Sham组维持双肺通气3 h,其余组均实施肺IR：左侧肺门夹闭1 h后松开无创血管夹恢复血流再通气2 h。D组泵入10μg·kg^-1右美托咪定负荷量后开始IR模型,DL组泵入0.3 mg·kg^-1 LY294002后泵入右美托咪定,待右美托咪定泵入完毕后开始IR模型。IR模型完毕后肺门离断处死大鼠,留取左肺组织,称重,计算肺湿干重比（W/D）;TUNEL法检测肺组织细胞凋亡情况;4%甲醛固定后HE染色分析肺损伤评分;Western-blot法检测磷酸化Akt（p-Akt）和HIF-1α蛋白表达水平。结果：与Sham组比较,其他3组肺组织W/D升高,肺损伤评分和凋亡指数升高,p-Akt和HIF-1α表达下调（P<0.05）;与IR组比较,D组和DL组肺W/D降低,肺损伤评分和凋亡指数降低,p-Akt和HIF-1α表达上调（P<0.05）;与D组比较,DL组肺W/D升高,肺损伤评分和凋亡指数降低升高,p-Akt和HIF-1α表达下调（P<0.05）。结论：PI3K/Akt/HIF-1α信号通路参与了右美托咪定减轻大鼠肺缺血再灌注损伤的过程。     

右美托咪定上调NLRC3改善大鼠机械通气相关性肺损伤

目的 观察右美托咪定对机械通气相关性肺损伤(VILI)大鼠NLR家族含CARD结构域蛋白3(NLRC3表达的影响。方法 36只SD大鼠随机分为正常对照组、模型组和右美托咪定组,每组各12只。接呼吸机机械通气制备VILI模型,右美托咪定组于制模前20 min静脉注射右美托咪定5μg·kg^-1,随后以5μg·kg^-1·h^-1的剂量维持。正常对照组和模型组于制模前20 min静脉持续输注生理盐水0.5 mL·kg^-1·h^-1。光镜下观察各组大鼠肺组织病理学结果,检测肺组织湿重-干重比。Western blot和qRT-PCR法分别检测肺组织中NLRC3、NLR家族热蛋白结构域包含蛋白3(NLRP3)、凋亡相关斑点蛋白(ASC)、caspase-1、NF-κB p65的蛋白和mRNA表达,ELISA法测定血清中白细胞介素(IL)-1β、IL-18和IL-33的浓度。结果 与正常对照组相比,模型组肺组织病理损伤严重,肺损伤定量评价指标(IQA)和肺组织湿重-干重比显著增加(P<0....     

右美托咪定对老年髋关节手术患者围术期的心肌保护作用

目的 探讨心排量监测下右美托咪定对髋关节手术老年患者心肌的影响.方法 选择2019年3月-2021年6月我院收治的行髋关节手术的老年患者共90例,随机数字表法分为对照组和右美托咪定组,每组45例.右美托咪定组给予静脉泵入右美托咪定(0.25μg/kg负荷量),并以0.25μg/(kg·h)的速率输注.对照组给予等容量生...     

前扣带回皮层中趋化因子CX3CL1对于大鼠慢性病理性疼痛的影响

目的观察大鼠在慢性疼痛时,前扣带回皮层(anterior cingulate cortex,ACC)中趋化因子CX3CL1的表达对于胶质细胞活化的影响。方法本实验采用大鼠左侧眶下神经结扎模型(unilateral infraorbital nerve,CCI-ION)。80只♂SD大鼠随机分为4组(n=20),分别为假手术组、疼痛组、PBS治疗对照组、CX3CL1中和抗体治疗组。假手术组仅暴露大鼠左侧眶下神经,不予结扎;疼痛组暴露大鼠左侧眶下神经并结扎。这2组分别于1、3、5、7、14 d早晨9∶00进行行为学测试,并且于行为学测试完成之后处死大鼠,取其前扣带回皮层,分别比较趋化因子CX3CL1和CD11b(小胶质细胞标记物)的表达水平。PBS治疗对照组是在眶下神经结扎术后CX3CL1表达水平最高的当天10∶00进行大鼠前扣带回皮层给药,给予PBS溶液。CX3CL1中和抗体治疗组与PBS治疗对照组同一天、同时间于大鼠前扣带回皮层给予CX3CL1中和抗体。两组于给药后6 h进行行为学测试,并于行为学测试完毕后处死大鼠,取前扣带回皮层组织,Western blot分别检测其中CD11b、CX3CL1、白细胞介素1β(IL-1β)的蛋白表达水平。结果各组大鼠术前行为学测试差异无统计学意义(P>0.05);假手术组、疼痛组术后两组相同时间行为学测试发现,疼痛组大鼠左侧V2区痛阈明显下降,差异有统计学意义(P<0.05);两组给药组给药后行为学测试发现给予CX3CL1中和抗体后,大鼠痛阈有明显提高,差异有统计学意义(P<0.05)。结论前扣带回皮层可能通过胶质细胞和趋化因子参与对慢性神经痛的调节。     

基于CX3CL1/CX3CR1轴探讨槲皮素对大鼠血管平滑肌细胞增殖的抑制作用

摘要：目的:基于人趋化因子Fractalkine （CX3CL1）/人趋化因子Fractalkine受体（CX3CR1）轴探讨槲皮素对大鼠血管平滑肌细胞（VSMC）增殖的抑制作用。方法:设VSMC细胞组、西拉普利组(100.0μg·ml-1)、槲皮素低、高剂量组(槲皮素终浓度分别为100.0,200.0μg·ml-1);各组每孔设6个平行样,培养72 h。培养结束后,CCK-8溶液试剂测定细胞增殖水平,结晶紫染色测定单克隆形成数目,流式细胞仪分析细胞凋亡水平,RT-PCR法及Western-Blot法测定细胞CX3CL1、CX3CR1基因和蛋白水平。结果:与VSMC细胞组比较,西拉普利组、槲皮素低、高剂量组吸光度（A）值、存活率、单克隆形成数目、CX3CL1、CX3CR 1mRNA和蛋白表达水平降低,而凋亡率升高（P<0.05）。与西拉普利组比较,槲皮素低剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平升高,而凋亡率降低（P<0.05）;槲皮素高剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平降低,而凋亡率升高（P<0.05）;且槲皮素高剂量组A值、存活率水平、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平低于槲皮素低剂量组,而凋亡率高于槲皮素低剂量组（P<0.05）。结论:在100.0～200.0μg·ml-1的范围内,槲皮素能抑制大鼠血管平滑肌细胞增殖,促进大鼠血管平滑肌细胞凋亡;其机制可能与槲皮素能抑制大鼠血管平滑肌细胞CX3CL1、CX3CR1 mRNA和蛋白表达水平进而抑制CX3CL1/CX3CR1轴的激活有关。     

CX3CL1/CX3CR1介导的血小板浸润抑制肝癌生长

目的探讨肝细胞肝癌(HCC)细胞衍生的CX3CL1介导的肝癌组织血小板浸润的作用和机制。方法我们利用体外Transwell细胞迁移实验和原位瘤及皮下荷瘤裸鼠模型,采用RNA干扰、流式检测、免疫荧光、免疫组化及Western印迹等方法。结果人和小鼠肝细胞癌(HCC)组织中有血小板浸润,HCC细胞衍生的CX3CL1直接诱导血小板迁移,缺氧通过上调CX3CL1表达而增强其迁移。体外Transwell实验发现敲除CX3CL1的HCC细胞减少了血小板迁移,在小鼠HCC原位移植模型中亦观察到此现象,且促进了肿瘤生长,在皮下荷瘤模型中,注射迁移的血小板导致HCC生长抑制。实验发现CX3CR1/Syk/PI3K参与了CX3CL1诱导的血小板迁移,迁移的血小板通过降低肝癌细胞线粒体膜电位和增加凋亡细胞的百分比来诱导HCC细胞凋亡。结论 HCC细胞衍生的CX3CL1诱导的血小板浸润抑制HCC生长。     

右美托咪定对结肠癌模型大鼠的治疗作用及对RhoA/ROCK1信号通路的影响

目的:探讨右美托咪定对结肠癌模型大鼠的治疗作用及对Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋蛋白激酶1(ROCK1)信号通路的影响.方法:通过1,2-二甲肼诱导建立结肠癌大鼠模型,将成模大鼠随机分为模型组,右美托咪定低(25μg/kg)、中(50μg/kg)和高(100μg/kg)剂量组,每组6只.另取6...     

右美托咪定在体外对原代海马神经元氧化应激损伤的影响

目的 探讨右美托咪定在体外减弱原代海马神经元的氧化应激损伤的机制.方法 将培养的原代海马神经元分为5组:空白对照组(C组)、损伤对照组(S组)、右美托咪定组(D组),D1,D2,D3组加入不同剂量的右美托咪定(0.001μmol/L、0.1μmol/L、10μmol/L).利用1 mmol/L的过氧化氢(H2O2)处理原代海马神经元1 h,制作神经元氧化应激损伤模型.按照以上分组情况加入右美托咪定,37℃、5％二氧化碳孵箱孵育6 h.通过测定细胞存活率和上清液中乳酸脱氢酶(LDH)的活性确定减轻海马神经元损伤的右美托咪定的适宜浓度.并检测细胞内丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性的变化.应用逆转录聚合酶链反应(RT-PCR)方法测量各组细胞外信号调节激酶(ERK)1/2和脑源性神经营养因子(BNDF)mRNA表达量.结果 右美托咪定组(0.001μmol/L、0.1μmol/L、10μmol/L)细胞存活率分别为(72.13±2.45)％、(89.34±2.56)％、(78.40±2.60)％,均高于损伤组的(51.04±2.12)％,差异有统计学意义(P<0.05);LDH活性显著低于损伤对照组;0.1μmol/L右美托咪定组对海马神经细胞氧化应激损伤的保护作用最好.0.1μmol/L右美托咪定组海马神经细胞培养上清液中MDA含量及细胞凋亡率显著低于损伤对照组,SOD活性显著高于损伤对照组.RT-PCR法检测结果提示0.1μmol/L右美托咪定组ERK1/2和BNDF mRNA表达量显著高于损伤对照组.结论 适宜剂量的右美托咪定对氧化应激损伤的海马神经元有一定的保护作用,其作用机制可能与其能够提升海马神经细胞的抗氧化能力,从而抑制海马神经元的凋亡有关,这种功能可能与ERK1/2和BNDF信号通路有关.     

右美托咪定预处理对大鼠心肌缺血再灌注损伤的保护作用及补体3蛋白的影响

目的：探讨右美托咪定预处理对大鼠心肌缺血再灌注损伤的保护作用及对补体3（C3）蛋白的影响。方法：sD雄性大鼠45只,随机分为3组（n=15）：假手术组（Sham组）、缺血再灌注组（I／R组）、右美托咪定预处理组（DEX组）。DEX组自缺血前2h持续静脉输注右美托咪定5mL·kg^-1（用0．9％氯化钠注射液将右美托咪定稀释为1gg·mL^-1）直到结扎心脏冠状动脉左前降支前停止,输注时间为2h;Sham组72．I／R组在相同的时间内按照5mL·kg^-1速率输注等量0．9％氯化钠注射液。再灌注120min时,取心脏组织,测定心肌梗死面积,用蛋白质印迹法（Westernblot）测定心肌组织中c3蛋白的表达。结果：与Sham组比较,I／R组和DEX组的心肌梗死面积、C3蛋白表达明显升高（P〈0．05）;与I／R组比较,DEX组的心肌梗死面积和C3蛋白表达明显降低（P〈0．05）。结论：右美托咪定预处理能够减轻大鼠心肌缺血再灌注损伤,其机制与减少补体3蛋白表达有关。     

Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(银杏蜜环口服溶液) attenuates inflammation of microglia in habenular nucleus throughCX3CL1-CX3CR1 axis in post stroke depression

OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye, YXMH), a representative drug for "Treating both Brain and Heart", showed considerable clinical effects in ischemic cardiovascular and cerebral vascular diseases. Recently, it is reported that YXMH has the potential for treating myocardial and cerebral ischemia related mental disorders, such as post stroke depression(PSD) and chronic heart disease(CHD) associated anxiety disorder. However, its mechanism has not been clearly elucidated. Meanwhile, increasing evidence revealed that there are close functional links between depression and habenular nucleus. The present study investigates the underlying mechanism of YXMH on attenuating the inflammation of microglia in habenular nucleus through CX3 CL1-CX3 CR1 axis in in a rat model of PSD. METHODS Rats were randomly devided into sham group,model group, Ginaton group(18 mg·kg~(-1)), Armillariella Mellea group(600 mg·kg~(-1)), Fluoxetine group(10 mg·kg~(-1)), YXMH high-dose group(618 mg·kg~(-1)) and YXMH low-dose group(309 mg·kg~(-1)). The PSD model was induced by transarterial microembolization combined with sleep deprivation(2-Chloro-D-phenylalanine, PCPA, IH, 200 mg·kg~(-1), for 3 times,before the behavior test) in SD male rats. Then rats were treated with corresponding medicaments through gavage once a day until 3 weeks later, followed by body mass measurement, neurological deficit score evaluation, gripping strength and thermal withdrawl latency measurement, as well as depression related behavioral indicators, the open field test(OFT) and sucrose preference test. The pathological morphological changes of habenular nucleus was observed by HE staining, the expression of IBA-1 was measured and analyzed by immunohistochemistry staining, and alterations of proteins and genes related to the CX3 CL1-CX3 CR1 axis were analyzed using Western blotting(CX3 CL1, CX3 CR1) and real-time polymerase chain reaction(PCR)(CX3 CL1, CX3 CR1). RESULTS Compared with the sham group, rats in the model group manifested as decreased body mass, deficient neurological behavior and gripping strength, reduced locomotor activity and sugar water consumption, as well as elevated thermal withdrawl latency(P<0.05, P<0.01). Meanwhile, the pathological morphology of the habenular nucleus on the ischemic hemisphere showed significant neuronal degeneration, microglial proliferation, inflammatory cells and glia cells infiltration, together with up-regualted expression of IBA-1, CX3 CL1, CX3 CR1 protein and CX3 CL1, CX3 CR1 mRNA. YXMH attenuated inflammation of microglia in habenular nucleus through improving pathological morphology, inhibiting IBA-1 activation, down-regulating the expression of CX3 CL1 and CX3 CR1 proteins and genes, and thus improved the behavior performance of ischemic injury and depression. CONCLUSION YXMH ameliorates neurological deficit and depressive behavior in rat model of PSD induced by transarterial microembolization combined with sleep deprivation, and the mechanism is probably related to attenu-ating inflammation of microglia in habenular nucleus through CX3 CL1-CX3 CR1 axis.     

CX3CR1 as a target for airways inflammation

Inflammation is a key component of asthma. Membrane-bound chemokine CX3CL1 is markedly induced on endothelial cells by inflammatory cytokines, and CX3CL1 levels are elevated in the bronchoalveolar lavage (BAL) of subjects with asthma. Recently, CX3CR1 (the receptor for CX3CL1) has been proposed as a target for airway inflammation, and the paper proposing this was evaluated. The paper established a link between CX3CR1 and asthma, as reducing the availability of CX3CR1, or inhibiting the responses mediated by the CX3CR1, resulted in reduced asthma in a mouse model. This suggests that agents blocking the CX3CR1 may be useful in the treatment of asthma. However, there are reports suggesting that glucocorticoids may downregulate the CX3CL1-CX3CR1 pathway in inflammation. Thus, the next step is to establish whether inhibitors of the CX3CL1-CX3CR1 pathway have any additional, or different, effects to glucocorticoids, in the treatment of airway inflammatory disorders, in animal models. Subsequently, further consideration can be given to the development of CX3CR1 as a target for airway inflammation in humans.     

Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway

Atherosclerosis is currently considered an inflammatory disease. Much attention has been focused on the potential role of inflammatory mediators as prognostic/diagnostic markers or therapeutic targets of atherosclerotic cardiovascular disease. CX3CL1 (or fractalkine) is a structurally and functionally unique chemokine with a well documented role in atherosclerosis. In its membrane bound form it promotes the firm adhesion of rolling leucocytes onto the vessel wall, while in its soluble form it serves as a potent chemoattractant for CX3CR1-expressing cells. Additionally, CX3CL1 exerts cytotoxic effects on the endothelium as well as anti-apoptotic and proliferative effects on vascular cells, affecting the context and stability of the atherosclerotic plaque. Studies on animal models have shown that the blockade of the CX3CL1/CX3CR1 pathway ameliorates the severity of atherosclerosis, while genetic epidemiology has confirmed that a genetically-defined less active CX3CL1/CX3CR1 pathway is associated with a reduced risk of atherosclerotic disease in humans. Although several studies support an important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization, this does not necessarily suggest that this pathway is a suitable therapeutic target or that CX3CL1 can serve as a prognostic/diagnostic biomarker. Further studies on the CX3CL1/CX3CR1 chemokine pathway are clearly warranted to justify the clinical relevance of its role in atherosclerosis.     

肝纤维化大鼠肝脏胸腺表达趋化因子和神经趋化蛋白的表达变化

目的:观察趋化因子胸腺表达趋化因子(CCL25)和神经趋化蛋白(CX3CLl)在正常大鼠肝脏组织和肝纤维化大鼠肝脏内的表达变化。方法:研究正常肝组、肝纤维化造模4周组和肝纤维化造模6周组,每组10例,以ELISA法测定大鼠肝脏组织中CCL25和CX3CL1的含量。结果:CCL25在正常肝组、肝纤维化造模4周组和肝纤维化造模6周组的含量分别为(5.1±1.4)ng/g、(11.5±3.3)ng/g、(15.2±3.5)ng/g,肝纤维化组的含量显著高于正常肝组。CX3CL1在正常肝组、肝纤维化造模4周组和肝纤维化造模6周组的含量分别为(3.1±1.3)ng/g、(9.9±2.5)ng/g、(10.4±2.7)ng/g,肝纤维化组的含量均显著高于正常肝组(P<0.01)。结论:趋化因子CCL25和CX3CLl在大鼠的正常肝组织中有表达,但表达的数量水平较低。肝脏发生纤维增生性损伤时,肝内CCL25和CX3CL1的含量都显著增加,随着病变由肝纤维化向肝硬化阶段发展,肝内CCL25和CX3CLl的含量呈现出不同变化,CCL25表现为进一步升高,CX3CL1表现为维持在高水平。     

Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices

This work reports the effect of chemokine fractalkine/CX3CL1, an endogenous small peptide highly expressed in the central nervous system, on evoked synaptic responses investigated in mouse CA1 stratum radiatum using an electrophysiological approach. We report that in acute mouse hippocampal slices, superfusion of CX3CL1 resulted in a reversible depression of the field excitatory postsynaptic potential (fEPSP) which developed within few seconds, increased for up to 10 min of application and disappeared within 30 min after the end of CX3CL1 treatment. We also show that CX3CL1-induced synaptic depression is (i) dose-dependent with IC50 and nH values of 0.7 nM and 1, respectively, (ii) not associated with a change in paired-pulse facilitation, (iii) mediated through CX3CL1 receptor (CX3CR1), being absent in CX3CR1-/- mice and inhibited in wild-type mice by a specific blocking antibody, and (iv) occluded by the induction of homosynaptic long-term depression (LTD). We conclude that CX3CL1 is a potent neuromodulator of the evoked excitatory synaptic transmission, sharing common mechanisms with LTD.     

右美托咪啶对肾脏缺血再灌注损伤大鼠肾组织血红素氧合酶-1表达的影响

目的评价右美托咪啶对肾脏缺血再灌注损伤大鼠肾组织血红素氧合酶-1表达的影响。方法健康Wistar大鼠36只,雌雄不限,体重300~350g,随机分为3组:假手术组(S组)、肾脏缺血再灌注组(IR组)和右美托咪啶组(D组),各12只。采用动脉压夹夹闭双侧肾动脉60min、恢复灌注4h建立大鼠肾脏缺血再灌注模型。D组于夹闭双侧肾动脉前10min尾静脉注射右美托咪啶3μg/kg;IR组于夹闭双侧肾动脉前10min尾静脉注射等容量生理盐水;S组不夹闭双侧肾动脉,分离肾动脉后尾静脉注射等容量生理盐水。术后再灌注4h时处死大鼠取肾组织,采用PCR技术检测血红素氧合酶-1mRNA的表达,Westernblot法测定血红素氧合酶-1(HO-1)蛋白水平,光镜下观察肾组织病理学结果。结果与S组比较,IR组和D组肾组织血红素氧合酶-1mRNA和HO-1蛋白的表达上调(P<0.05);与IR组比较,D组肾组织血红素氧合酶-1mRNA和HO-1蛋白的表达上调(P<0.05),肾组织病理学损伤减轻。结论右美托咪啶减轻大鼠肾脏缺血再灌注损伤与其上调肾组织血红素氧合酶-1的表达有关。     

Therapeutic potential of the chemokine–receptor duo fractalkine/CX3CR1: an update

Introduction: The chemokine fractalkine/CX3CL1 and its highly selective receptor CX3CR1 mediate critical physiological events during inflammatory responses. The fractalkine/CX3CR1 axis has been shown to play a key role in the pathogenesis and the progression of a large number of diseases in which imbalance of the immune response is frequently seen. Since our last review published in early 2010, the fractalkine/CX3CR1 axis has gained vast attention as a potential therapeutic target in the scientific community, which can be clearly seen in the large number of studies that have been published on this issue since then.

Areas covered: A Medline/PubMed search was performed to detect all recently published studies on the role of the fractalkine/CX3CR1 axis as a therapeutic target in a wide range of clinical diseases.

Expert opinion: Recently published studies further underline the high potential of the fractalkine/CX3CR1 axis as a major target for future treatment of pain, inflammation and cancer. However, no clinical trials on novel therapeutics targeting fractalkine or CX3CR1 have been initiated so far, so that the fractalkine/CX3CR1 axis does still not find application in daily clinical practice.     

Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique therapeutic potential

Importance of the field: Fractalkine, also known as CX3CL1, is the unique member of the fourth class of chemokines and mediates both chemotaxis and adhesion of inflammatory cells via its highly selective receptor CX3CR1. Fractalkine mediates inflammatory responses and pain sensation and is involved in the pathogenesis and progression of numerous inflammatory disorders and malignancies.

Areas covered in this review: We performed a Medline/PubMed search to detect all published studies that explored the role of fractalkine and CX3CR1 and the possibilities of therapeutic intervention in the fractalkine/CX3CR1 axis in a wide range of clinical disorders, using CX3CR1 blocking antibodies, different fractalkine antagonists, CX3CR1 depletion or transfection of fractalkine expression vectors.

What the reader will gain: This review summarizes the role of fractalkine and its receptor CX3CR1 in various diseases, focusing on their high potential as novel therapeutic targets, with special emphasis on pancreatic diseases.

Take home message: The reviewed studies provide promising results demonstrating fractalkine and CX3CR1 as potential target molecules for future therapeutics that may attenuate pain, inflammation and furthermore serve as an anti-cancer therapy. However, to date, no therapeutics targeting fractalkine or CX3CR1 are in clinical use.