CXCL1/CXCR2在羊瘙痒因子感染小鼠脑组织中的分布特征研究

目的 探究朊病毒感染小鼠脑组织CXC趋化因子配体1 (CXCL1)与CXC趋化因子受体2 (CXCR2)的分布特征。方法 通过免疫组织化学、免疫组织荧光双染实验明确羊瘙痒因子139A及ME7感染终末期小鼠脑组织中CXCL1/CXCR2的分布特征,确定CXCL1/CXCR2的靶细胞及与羊瘙痒因子样朊蛋白(PrPSc)沉积的关系。结果 通过全脑区免疫组化染色发现,CXCL1/CXCR2在羊瘙痒因子139A及ME7感染终末期小鼠脑组织中的含量明显升高,主要分布在海马、皮层、丘脑、小脑及延髓5个脑区。CXCL1与小胶质细胞和神经元细胞存在共定位,而CXCR2与神经元细胞存在共定位。在羊瘙痒因子139A及ME7感染终末期小鼠脑组织中CXCL1、CXCR2和PrP^Sc三者存在明显共定位。结论 CXCL1/CXCR2分布于朊病毒感染小鼠脑组织中朊病毒病理特征集中的脑区。     

糖尿病痛性周围神经病变大鼠脊髓小胶质细胞Toll样受体3的变化

目的：观察糖尿病痛性周围神经病变大鼠脊髓小胶质细胞Toll样受体3（TLR3）的变化。方法：雄性SD大鼠,采用腹腔注射链尿佐菌素（STZ）制备糖尿病痛性周围神经病变模型。取造模成功的大鼠10只作为糖尿病组（D组）,取10只同月龄腹腔注射0.9%氯化钠液大鼠为对照组（C组）。观测2组大鼠的血糖水平和行为学评分,并应用免疫荧光双标记和激光共聚焦显微镜技术比较各组脊髓背角TLR3的变化。结果：与C组比,D组血糖在注射STZ2d后显著升高;在注射STZ后14～28d机械缩足阈值（mechanical withdrawal threshold,MWT）降低;注射STZ后28d,D组TLR3表达显著上调并且主要与小胶质细胞共标。结论：小胶质细胞TLR3可能参与了糖尿病周围神经痛的发生。     

降糖明目汤对糖尿病小鼠模型血糖及体质量的影响研究

目的通过观察降糖明目汤对经链脲佐菌素(STZ)诱导的C57BL/B小鼠糖尿病模型血糖及体质量的影响,探讨其对糖尿病视网膜病变治疗作用的机制。方法40只C57BL/B小鼠,随机分为A组:正常对照组、B组:正常小鼠喂中药组、C组:糖尿病小鼠模型组、D组:糖尿病小鼠模型喂中药组。应用链脲佐菌素(STZ)诱导的C57BL/B小鼠糖尿病模型,于造模后1d、7d、30d、60d、80d测量并记录空腹尾血糖并称量体质量。结果经STZ诱导糖尿病成模后,糖尿病模型C组血糖较糖尿病模型给药D组高,但差异无统计学意义(P>0.05)。糖尿病模型C组体重较糖尿病模型给药D组低,但差异无统计学意义(P>0.05)。结论临床应用证实,降糖明目汤对早期糖尿病视网膜病变有治疗作用。本实验观察可见降糖明目汤对糖尿病小鼠血糖及体质量的改善并不显著,说明降糖明目汤并非通过降低血糖而对糖尿病视网膜病变起到治疗作用。因此该药物对糖尿病视网膜病变的抑制作用尚需进一步试验探究。     

骨痛灵方通过抑制整合素αvβ3通路缓解肺癌骨转移癌性疼痛

目的：探讨骨痛灵(Gutongling, GTL)方治疗肺癌骨转移疼痛的潜在作用机制。方法：将50只C57BL/6雄性小鼠随机分为5组(n=10)：假手术组（Sham组）、模型组（Model组）、唑来膦酸组（ZA组）、骨痛灵组（GTL组）、骨痛灵+唑来膦酸组（GTL+ZA组）。除Sham组给予接种PBS溶液外,其余各组均予鼠源肺腺癌细胞Lewis-LUC悬液造模。采用von Frey纤维丝测痛仪检测小鼠足底的机械痛阈值,共聚焦显微镜观察破骨细胞伪足小体F-actin环,实时荧光定量PCR法与免疫组化法检测各组小鼠左后肢胫骨骨组织中整合素αvβ3、富含脯氨酸的酪氨酸激酶2 (PyK2)、酪氨酸激酶Src、Casitas B细胞淋巴瘤家族蛋白(Cb1) mRNA及蛋白表达水平。结果：与Sham组比较,Model组小鼠造模后机械痛阈值下降(P <0.05)。造模后第14天：各给药干预组机械痛阈值较Model组升高(P <0.05);ZA组与GTL组机械痛阈值相当;造模后第21天：GTL+ZA组机械痛阈值较各给药组明显升高(P <0.05)。与Sham组比较,Model组F-...     

链脲佐菌素诱导建立C57BL/6小鼠1型糖尿病心肌病模型的可行性研究

目的:建立C57BL/6小鼠1型糖尿病心肌病模型,并评价该疾病模型的可行性.方法:70只小鼠随机分为模型组(n=43)和对照组(n=27).模型组小鼠按50mg/kg体重连续5 d腹腔注射链脲佐菌素(STZ)溶液,对照组小鼠注射相应体积的柠檬酸缓冲液.每周观察小鼠食量、饮水量、体重、精神活动等基本状况.每2周剪鼠尾取血,检测血糖,评价建模情况.实验第13用处死小鼠,取心脏石蜡包埋,行HE染色、天狼猩红染色显示病理改变,Image-pro plus 6.0分析软件计算胶原面积占总面积比值.结果:模型组小鼠饮水量、食量分别自第2、3周开始高于对照组小鼠(均P<0.01);注射STZ后第2周体重逐渐减轻,低于对照组小鼠(P<0.01).空腹血糖在建模第1周开始,模型组明显高于对照组(P<0.001).HE染色及天狼猩红染色显示模型组小鼠心肌纤维排列紊乱,分布不均,肌细胞间质明显增加.结论:本实验成功建立了C57BL/6小鼠1型糖尿痛心肌病模型,该模型可行性强,稳定性好.     

STZ诱导C57BL小鼠T1DM模型优化的研究

目的探索制备T1DM小鼠模型优化条件，为研究T1DM病因及发病机理提供理想的动物模型。方法分另9应用不同剂量、不同性另0小鼠以小剂量、多次注射链脲佐菌素方法（multiple low dose of stxeptozotodn，MLDS）制备T1DM小鼠糖尿病模型，动态监测小鼠血糖水平、体重的变化，比较不同方法糖尿病模型成功率与糖尿病小鼠死亡率。结果MLDS诱导雌性C57BL小鼠T1DM模型STZ小剂量组模型成功率为0，死亡率为22．06％。STZ大剂量组模型成功率为57．14％。死亡率为28．56％；MLDS诱导C57BL雄性小鼠T1DM模型的结果，T1DM组小鼠模型成功率为75％，死亡率为20％；MLDS诱导雄性C57BL小鼠T1DM模型再研究结果，T1DM组小鼠模型成功率为84．6％，死亡率为0。结论C57BL雄性小鼠更适合用于制备MLDS诱导T1DM模型，65mg／kg．BW STZ造模剂量优于其它三种剂量。     

胰岛素抵抗小鼠脂肪组织肿瘤坏死因子α和脂联素mRNA表达与有氧运动的影响

背景：有研究表明有氧运动可通过调节脂肪组织过氧化物酶体激活物增殖受体γ及其相关脂肪因子进而影响胰岛素敏感性,但其影响结果及作用机制至今少有报道。目的：观察有氧运动后,胰岛素抵抗C57BL/6小鼠脂肪组织过氧化物酶体激活物增殖受体γ、肿瘤坏死因子α和脂联素mRNA及蛋白表达水平的变化,分析有氧运动对胰岛素抵抗小鼠影响的作用机制。方法：C57BL/6小鼠经高脂饮食喂养10周后建立胰岛素抵抗动物模型,建模后将小鼠随机分为安静组与运动组。运动组进行为期6周,75%VO2max强度跑台运动;安静组同等条件下饲养不运动。使用RT-PCR和Western blot法检测两组脂肪组织过氧化物酶体激活物增殖受体γ,脂联素、肿瘤坏死因子αmRNA和蛋白表达。结果与结论：6周有氧跑台运动对小鼠脂肪组织过氧化物酶体激活物增殖受体γ表达差异无显著性意义（P〉0.05）,但可显著增加小鼠脂肪组织脂联素的表达（P〈0.01）,降低肿瘤坏死因子α的表达（P〈0.05）;并且可显著降低血液中三酰甘油、游离脂肪酸水平（P〈0.05,P〈0.01）。结果提示有氧运动可能通过调节过氧化物酶体激活物增殖受体γ相关脂肪因子-脂联素和肿瘤坏死因子α的表达来间接调节脂肪组织对胰岛素的敏感性。有氧运动可以显著增加机体组织对胰岛素的敏感性,从而改善C57BL/6小鼠胰岛素抵抗的症状。     

Toll样受体4参与调控脂质诱导的平滑肌细胞炎症反应的研究

目的:探究Toll样受体4(Toll-like receptor 4,TLR4)调控脂质诱导平滑肌炎症反应的机制。方法 :使用TLR4敲除小鼠(以野生型C57BL/6小鼠为对照),随机分组为对照组(普通饲料)和实验组(高脂饲料喂养),每组各6只,12周后观察动脉斑块进展情况。体外培养TLR4基因敲除小鼠(以野生型C57BL/6小鼠为对照)的原代平滑肌细胞。此外,使用TLR4特异性抗体阻断TLR4活性后,观察氧化型低密度脂蛋白(oxidized low density lipoprotein,ox LDL)刺激下炎症因子反应。结果 :高脂喂养可显著促进野生型小鼠主动脉平滑肌细胞炎症因子表达,而高脂喂养TLR4基因敲除小鼠平滑肌细胞中炎症因子表达水平无明显升高;TLR4特异性抗体可抑制ox LDL诱导的炎症反应。结论:Toll样受体4通过上调平滑肌细胞中炎症因子水平参与ox LDL诱导的炎症反应。     

三阴乳癌组织CXCL12与CXCR4表达及其意义

目的探讨趋化因子CXCL12及其受体CXCR4在三阴乳癌（TNBC）组织表达及其临床病理学意义。方法采用免疫组化SP法检测CXCL12和CXCR4蛋白在55例TNBC组织中的表达,观察相应的临床病理指标（病人年龄、肿瘤大小、淋巴结转移情况、临床分期）,并进行相关性分析。结果 TNBC组织CXCL12、CXCR4表达与病人年龄、肿瘤大小和临床分期无明显相关性（P〉0.05）,而与腋窝淋巴结转移状态呈正相关（r=0.413、0.325,P〈0.05）,淋巴结有转移组CXCL12、CXCR4的表达明显强于淋巴结无转移组（uc=3.02、2.38,P〈0.05）。结论推测CXCL12及CXCR4可作为预测TNBC腋窝淋巴结转移及预后的一个重要分子标志物。     

补体C3对神经病理性疼痛模型脊髓星形胶质细胞的影响

目的:观察补体C3对神经病理性疼痛模型脊髓星形胶质细胞的影响。方法:81只补体C3基因敲除小鼠随机分三组(n=27):A组:假手术组;B组:慢性坐骨神经结扎模型(CCI)组;C组:CCI模型补体C3干预组。测定小鼠的热痛阈值和机械痛阈值,并取腰5、6脊髓节段测定GFAP mRNA和GFAP表达。结果 :术前三个组小鼠热和机械痛阈无明显差异,术后1天A组热和机械痛阈下降,其后恢复。B组和C组继续下降,C组下降幅度更大(P<0.05)。术后第1天,B组和C组胶质细胞激活轻微,术后第3、7天B组和C组脊髓组织GFAP mRNA和GFAP表达量逐渐增加,且C组其表达量明显高于B组。结论 :补体C3的存在与神经病理性模型小鼠星形胶质细胞激活显著相关,并由此影响到慢性疼痛状态的出现和维持。     

Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury

Mortality related to adult respiratory distress syndrome (ARDS) ranges from 35% to 65%. Lung-protective ventilator strategies can reduce mortality during ARDS. The protective strategies limit tidal volumes and peak pressures while maximizing positive end-expiratory pressure. The efficacy of this approach is due to a reduction of shear-stress of the lung and release of inflammatory mediators. Ventilator-induced lung injury (VILI) is characterized by inflammation. The specific mechanism(s) that recruit leukocytes during VILI have not been elucidated. Because the murine CXC chemokines KC/CXCL1 and MIP-2/CXCL2/3, via CXCR2, are potent neutrophil chemoattractants, we investigated their role in a murine model of VILI. We compared two ventilator strategies in C57BL/6 mice: high peak pressure and high stretch (high peak pressure/stretch) versus low peak pressure/stretch for 6 hours. Lung injury and neutrophil sequestration from the high-peak pressure/stretch group were greater than those from the low-peak pressure/stretch group. In addition, lung expression of KC/CXCL1 and MIP-2/CXCL2/3 paralleled lung injury and neutrophil sequestration. Moreover, in vivo inhibition of CXCR2/CXC chemokine ligand interactions led to a marked reduction in neutrophil sequestration and lung injury. These findings were confirmed using CXCR2(-/-) mice. Together these experiments support the notion that increased expression of KC/CXCL1 and MIP-2/CXCL2/3 and their interaction with CXCR2 are important in the pathogeneses of VILI.     

CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5

Recent studies have implicated chemokines in microglial activation and pathogenesis of neuropathic pain. C-X-C motif chemokine 13 (CXCL13) is a B lymphocyte chemoattractant that activates CXCR5. Using the spinal nerve ligation (SNL) model of neuropathic pain, we found that CXCL13 was persistently upregulated in spinal cord neurons after SNL, resulting in spinal astrocyte activation via CXCR5 in mice. shRNA-mediated inhibition of CXCL13 in the spinal cord persistently attenuated SNL-induced neuropathic pain. Interestingly, CXCL13 expression was suppressed by miR-186-5p, a microRNA that colocalized with CXCL13 and was downregulated after SNL. Spinal overexpression of miR-186-5p decreased CXCL13 expression, alleviating neuropathic pain. Furthermore, SNL induced CXCR5 expression in spinal astrocytes, and neuropathic pain was abrogated in Cxcr5^–/– mice. CXCR5 expression induced by SNL was required for the SNL-induced activation of spinal astrocytes and microglia. Intrathecal injection of CXCL13 was sufficient to induce pain hypersensitivity and astrocyte activation via CXCR5 and ERK. Finally, intrathecal injection of CXCL13-activated astrocytes induced mechanical allodynia in naive mice. Collectively, our findings reveal a neuronal/astrocytic interaction in the spinal cord by which neuronally produced CXCL13 activates astrocytes via CXCR5 to facilitate neuropathic pain. Thus, miR-186-5p and CXCL13/CXCR5-mediated astrocyte signaling may be suitable therapeutic targets for neuropathic pain.     

滤泡辅助性T细胞在急性肝衰竭小鼠模型中的变化及意义

目的:探讨滤泡辅助性T(T follicular helper,Tfh)细胞及相关细胞因子白细胞介素(interleukin,IL)-21在急性肝衰竭(acute liver failure,ALF)小鼠模型中的变化及意义。方法:将20只雌性C57BL/6小鼠随机分成2组,分别予脂多糖/D-氨基半乳糖或磷酸盐缓冲液(phosphate buffer solution,PBS)腹腔注射,6 h后采集血液、肝脏和脾脏组织标本。采用苏木精-伊红染色法分析肝脏病变情况;流式细胞术分析小鼠脾脏单个核细胞中Tfh细胞的频数;酶联免疫吸附试验分析血清中IL-21和肿瘤坏死因子α(tumor necrosis factorα,TNF-α)的水平。结果:ALF小鼠肝脏肿大而呈暗红色,肝细胞大量坏死和炎性细胞浸润,其血清中TNF-α及IL-21的水平均较正常对照组显著增高(P<0.01,P<0.05);而单个核细胞中CD4+CXCR5+、CD4+PD-1+、CD4+CXCR5+PD-1+T细胞频数亦较正常对照组显著升高(P<0.01)。结论:ALF小鼠脾脏单个核细胞中Tfh细胞频数显著增加,血清IL-21水平显著升高,推测Tfh细胞在ALF的发病过程中起重要作用,本研究结果可能为ALF的治疗提供新思路。     

人结直肠癌趋化因子配体生物轴及干细胞标志物基因表达与临床病理

背景：趋化因子配体12/趋化因子受体4生物学轴在肿瘤的特异性转移中有重要作用,而干细胞标志物糖蛋白激素受体5基因的表达对于肿瘤的增殖和侵袭转移发挥重要作用。 目的：观察趋化因子配体12/趋化因子受体4生物轴以及干细胞标志物糖蛋白激素受体5基因在人结直肠癌组织中的表达变化及其与临床中的病理特征的关系。 方法：收集2013年1至6月辽宁省肿瘤医院收治100名结直肠癌患者为实验组,100名健康体检者为对照组,采用免疫组织化学SP法检测两组组织中趋化因子配体12、趋化因子受体4及干细胞标志物糖蛋白激素受体5 mRNA表达情况,并分析趋化因子配体12、趋化因子受体4及干细胞标志物糖蛋白激素受体5 mRNA表达与结直肠癌患者年龄、性别、肿瘤大小及部位、淋巴转移以及预后等临床病理特征的相关性。 结果与结论：趋化因子受体4、糖蛋白激素受体5 mRNA在结直肠癌组织中均有较高的表达率,但是趋化因子配体12 mRNA表达率降低。趋化因子受体4、干细胞标志物糖蛋白激素受体5 mRNA、趋化因子配体12 mRNA三者与结直肠癌患者的年龄、性别等患者临床特征无相关性,与结直肠癌的发病位置及其大小也无相关性,与结直肠癌组织是否淋巴转移具有相关性关,伴有淋巴转移的结直肠癌组织中干细胞标志物糖蛋白激素受体5 mRNA和趋化因子受体4的表达率更高,而趋化因子配体12 mRNA表达无显著变化;趋化因子受体4表达随肿瘤的恶性程度增高而增高;糖蛋白激素受体5表达于胃肠道肿瘤和脑肿瘤干细胞等表面,其表达随肿瘤的恶性程度增高而增高。提示结直肠癌组织中趋化因子受体4的表达增高,糖蛋白激素受体5基因表达增高,二者增高促进了结直肠癌组织生长及转移,糖蛋白激素受体5以及趋化因子配体12/趋化因子受体4轴的表达的调控,使其或将成为肿瘤诊断及治疗的重要新靶点。     

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown that CXCL10/CXCR3 interactions drive effector Th1 polarization via STAT1, STAT4, and STAT5 phosphorylation, while CXCL11/CXCR3 binding induces an immunotolerizing state that is characterized by IL-10^hi (Tr1) and IL-4^hi (Th2) cells, mediated via p70 kinase/mTOR in STAT3- and STAT6-dependent pathways. CXCL11 binds CXCR3 with a higher affinity than CXCL10, suggesting that CXCL11 has the potential to restrain inflammatory autoimmunity. We generated a CXCL11-Ig fusion molecule and evaluated its use in the EAE model of inflammatory autoimmune disease. Administration of CXCL11-Ig during the first episode of relapsing EAE in SJL/J mice not only led to rapid remission, but also prevented subsequent relapse. Using GFP-expressing effector CD4⁺ T cells, we observed that successful therapy was associated with reduced accumulation of these cells at the autoimmune site. Finally, we showed that very low doses of CXCL11 rapidly suppress signs of EAE in C57BL/6 mice lacking functional CXCL11.     

调节性DC分泌exosomes对急性GVHD抑制作用的初步研究

目的探讨调节性树突状细胞（rDC）分泌exosomes在移植物抗宿主病（GVHD）模型中的免疫抑制作用。方法用TGF-β1和IL-10诱导从C57BL／6小鼠骨髓来源产生rDC,负载DBA／2小鼠来源的抗原,应用流式检测rDC表型。采用超速离心结合膜超滤的方法分离纯化rDC分泌的exosomes,电镜检测exosomes形态。在以DBA／2小鼠为受鼠,C57BL／6小鼠为供鼠的急性GVHD模型中,尾静脉注射rDC分泌的exosomes,观察受鼠急性GVHD症状的改变。结果rDC的I—A／I—E（MHC一Ⅱ类分子）,共刺激分子CD80、CD86表达量均比未成熟树突状细胞（imDC）低,其分泌的exosomes为直径小于100nm的小囊泡。在小鼠急性GVHD模型中,同种异基因骨髓移植0、7、14d静脉注射rDex（15μg／只）治疗的小鼠,GVHD表现较对照组症状轻,生存期较长,两组相比差异有统计学意义（P〈0．05）;且较静脉注射rDex30pg／只的治疗效果好。结论rDC分泌的exosomes能够提高GVHD小鼠生存率,可应用于治疗急性GVHD。     

Th17细胞和白介素-17在异基因造血干细胞移植aGVHD中的免疫调控分析

目的探讨Th17细胞和白介素-17(IL-17)在异基因造血干细胞移植(allo-HSCT)aGVHD中的免疫调控。方法采用野生型(WT)C57BL/6(H-2b)小鼠与C57BL/6(H-2b)IL-17基因敲除(IL-17-/-)小鼠作为供体,采用BALB/C(H-2b)小鼠作为受体,小鼠给予全身照射8.5 Gy进行清髓性预处理,移植野生型(WT)小鼠1×107个去除T细胞骨髓细胞(TCD-BMCs)以及WT小鼠1×106个CD4+IL-17-/-T细胞。移植之后每天对小鼠生存状况进行观察1~2次,每隔5 d对aGVHD进行临床评估。收集实验小鼠肝脏、肺、肠以及皮肤,并进行HE染色并进行病理组织学分析,并对移植后Th17细胞组、CD4+IL-17-/-T细胞组、IL-17-/-BMCs+IL-17-/-SCs组(KK组)、WT BMCs+IL-17-/-SCs组(WK组)及WT BMSCs+WTSCs组(WW组)小鼠的aGVHD积分进行评估。结果 1Th17细胞组移植后5 d、10 d、15 d、20 d aGVHD积分均显著高于IL-17-/-CDD4+T细胞组(P0.05),且Th17细胞组小鼠平均生存时间显著小于IL-17-/-CDD4+T细胞组(P0.05);2KK组、WK组及WW组移植后5 d、10 d、15 d、20 d aGVHD积分差异均具有统计学意义(P0.05),且三组平均生存时间方面的差异也均具有统计学意义(P0.05)。结论 Th17细胞与IL-17在异基因造血干细胞移植aGVHD中具有较好的免疫调控作用。     

Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice

In humans, there is large inter-individual variability in the evolution of NAFLD (non-alcoholic fatty liver disease) to NASH (non-alcoholic steatohepatitis). To investigate this issue, NASH was induced with an MCD (methionine-choline-deficient) diet in C57BL/6 and Balb/c mice that are characterized by different biases in Th1/Th2 and macrophage (M1/M2) responses. Following 4?weeks on the MCD diet, steatosis and lobular inflammation were prevalent in C57BL/6 (Th1, M1 oriented) than in Balb/c (Th2, M2 oriented) mice. Consistently, hepatic TNFα (tumour necrosis factor α) mRNA expression and circulating TNFα levels were higher in MCD-fed C57BL/6 than in MCD-fed Balb/c mice. The Th1/Th2 bias did not account for the increased NASH severity, as in both strains MCD feeding did not significantly modify the liver mRNA expression of the Th1 markers IFNγ (interferon γ) and T-bet or that of the Th2 markers IL-4 (interleukin 4) and GATA-3. Conversely, MCD-fed C57BL/6 mice displayed higher liver mRNAs for the macrophage M1 activation markers iNOS (inducible NO synthase), IL-12p40 and CXCL10 (CXC chemokine ligand 10) than similarly treated Balb/c mice, without effects on the M2 polarization markers IL-10 and MGL-1 (macrophage galactose-type C-type lectin-1). Circulating IL-12 was also higher in MCD-fed C57BL/6 than in MCD-fed Balb/c mice. The analysis of macrophages isolated from the livers of MCD-fed animals confirmed an enhanced expression of M1 markers in C57BL/6 mice. Among all of the MCD-treated mice, liver iNOS, IL-12p40 and CXCL10 mRNA levels positively correlated with the frequency of hepatic necro-inflammatory foci. We concluded that the macrophage M1 bias in C57BL/6 mice may account for the increased severity of NASH in this strain, suggesting macrophage responses as important contributors to NAFLD progression.