当归多糖延缓D-半乳糖所致巢蛋白-绿色荧光蛋白小鼠脑衰老作用及其机制

目的探讨当归多糖(ASP)延缓D-半乳糖(D-Gal)所致巢蛋白(Nestin)-绿色荧光蛋白(GFP)小鼠脑衰老作用及可能机制。方法 6~8周龄雄性Nestin-GFP转基因小鼠40只,随机分为正常组(n=10)、ASP正常组(n=10)、脑衰老模型组(n=10)、ASP脑衰老模型组(n=10)。脑衰老模型组:小鼠皮下注射D-gal 200 mg/kg qd×42 d;ASP脑衰老模型组:从脑衰老模型建立的16d起腹腔注射ASP 140 mg/kg qd×27 d;ASP正常组:皮下注射等量生理盐水,第16天起腹腔注射ASP(剂量与时间同上);正常组:小鼠皮下注射等量生理盐水42d。模型建立完成第2天水迷宫实验检测各组小鼠的空间记忆能力;取海马制备冷冻切片,观察海马区神经干细胞荧光强度;衰老相关β-半乳糖苷酶(SA-β-Gal)染色观察海马组织中染色阳性细胞百分率;酶标比色法检测海马区超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和丙二醛(MDA)含量;酶联免疫吸附测定(ELISA)检测海马区白细胞介素(IL)-1β,IL-6和肿瘤坏死因子(TNF)-α炎症因子变化。结果脑衰老模型组小鼠空间记忆能力减退,海马齿状回(DG区)荧光强度降低,SA-β-Gal染色阳性颗粒增加,海马组织SOD活性和T-AOC降低,MDA含量升高,IL-1β,IL-6和TNF-α含量增多。与脑衰老模型组比较ASP脑衰老模型组小鼠空间记忆能力有明显改善,海马DG区荧光强度增强,SA-β-Gal染色阳性颗粒减少,海马组织SOD活性和T-AOC升高,MDA含量降低,IL-1β,IL-6和TNF-α含量减少。结论 ASP能延缓D-Gal所致小鼠脑衰老,其机制可能与抑制氧化应激损伤、下调炎症因子水平、维持海马区神经干细胞数量有关。     

盐酸小檗碱通过抑制TNF-α/caspase-8/caspase-3信号通路减轻急性低氧暴露引起的肝损伤

目的 研究盐酸小檗碱(BBR)对急性低氧暴露后肝脏的保护作用及相关机制.方法 C57BL/6小鼠分为常氧组、低氧暴露组、低氧暴露联合BBR组.实验第7天处死小鼠,取肝脏组织.称量小鼠及肝组织的质量,利用HE染色观察肝组织病变情况,利用实时定量PCR检测肝组织白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF...     

四氢嘧啶类衍生物ZL-5015抗内毒素作用的实验研究

目的:探讨1,3-二环戊基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯(ZL-5015)对内毒素攻击小鼠的保护作用及机制。方法:腹腔注射脂多糖(70 mg/kg)制备小鼠内毒素中毒死亡模型和内毒素血症模型。脂多糖(10mg/L)刺激小鼠腹腔巨噬细胞产生炎症相关细胞因子作为体外炎症模型。ELISA法检测细胞白细胞介素1β(IL-1β)、白细胞介素10(IL-10)和肿瘤坏死因子α(TNF-α)的含量。Real-time PCR检测细胞因子mRNA的表达水平。结果:ZL-5015(100和200 mg/kg)预防性灌胃给药能小幅提高内毒素中毒小鼠的存活率和存活时间,在中毒早期能降低内毒素血症小鼠血清中IL-1β和TNF-α的水平,提高IL-10的水平。体外实验表明,ZL-5015(10、20和40μmol/L)能抑制内毒素刺激的腹腔巨噬细胞IL-1β和TNF-α蛋白及mRNA的表达,促进IL-10蛋白及mRNA的表达。结论:四氢嘧啶类化合物ZL-5015能提高内毒素中毒小鼠的存活率和存活时间,但作用较弱,其作用机制可能与抑制促炎细胞因子IL-1β和TNF-α、促进抑炎细胞因子IL-10的表达有关。     

APP/PS1双转基因AD小鼠术后认知功能紊乱及其机制

目的探究阿尔茨默海病(AD)双转基因小鼠(APP/PS1)在麻醉手术后不同时程的认知功能改变及其可能的机制。方法将APP/PS1小鼠随机分为对照组(不予手术麻醉干预)和实验组(2.5%七氟烷麻醉下行剖腹探查术)。术后1和3 d行条件恐惧实验评估小鼠认知功能;并分别在术后12及24 h和3 d用酶联免疫吸附实验检测海马组织炎性因子IL-6、IL-1β、TNF-α及淀粉样蛋白Aβ_(42)蛋白含量;用Western blot检测α-突触核蛋白的表达。结果与对照组相比,实验组小鼠在术后1和3 d,与场景有关的僵直时间均显著减少。术后24 h实验组小鼠海马组织内IL-1β、IL-6及TNF-α的含量显著高于对照组(P0.05);同时Aβ_(42)蛋白和α-突触核蛋白的表达在术后24 h也显著上调(P0.05)。结论 AD双转基因小鼠接受麻醉手术后,在术后早期即可出现认知功能障碍,其发生机制可能与海马区α-突触核蛋白与Aβ_(42)表达异常及神经炎性反应相关。     

小鼠杏仁内侧核中白细胞介素1β的表达调控依赖于雌激素受体α(英文)

研究雌激素受体 ( ER)敲除小鼠脑内 ,ERα和 ERβ在介导内侧杏仁核中白细胞介素 1β( IL -1β)表达的作用。IL-1β表达有显著的性别差异 ,并且在 ER敲除小鼠含量减少。细菌脂多糖 ( L PS)或卵巢切除能够促进野生型和 ERβ敲除小鼠 ( BERKO) IL-1β表达 ,但对 ERα敲除小鼠 ( ERKO)无作用。相似的是 ,外源性雌激素能抑制野生型和 BERKO小鼠 IL -1β表达 ,后者时间稍有延搁 ,但对 ERKO IL-1β表达没有影响。结果表明 ,ERα是内侧杏仁核 IL -1β表达调节的重要机制 ,提示 ERs可作为选择性靶基因治疗和预防神经功能失常     

短管兔耳草总黄酮降低阿尔茨海默病模型小鼠大脑皮层及海马组织炎性细胞因子的水平

目的探讨短管兔耳草总黄酮(TF-LBM)治疗阿尔茨海默病(AD)的作用机制。方法 8月龄SAMP8小鼠50只,随机分为模型组,阳性药物组,低、中、高剂量TF-LBM组5组,每组10只;8月龄SAMR1小鼠10只为正常老化组。低、中、高剂量TF-LBM组以(150、300、600)mg/kg TF-LBM灌胃,阳性药物组以0.65 g/kg盐酸多奈哌齐灌胃,模型组和正常老化组用溶解TF-LBM等量蒸馏水灌胃。8周后,进行Morris水迷宫实验,计算各组小鼠定位航行潜伏期。行为学实验后进行取材,分别取各组小鼠大脑皮层组织及海马CA1区组织进行检测,应用放射免疫法检测药物对小鼠大脑皮层及海马白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量的影响。结果短管兔耳草总黄酮对小鼠行为学干预结果观察:与模型组相比,正常老化组、阳性药物组、高剂量组小鼠逃逸潜伏期明显缩短;与正常老化组相比,模型组小鼠皮层组织中IL-1β、IL-6、TNF-α显著增高;与模型组相比,低剂量TF-LBM组IL-1β含量无明显差异,而中剂量TF-LBM组、高剂量TF-LBM组及阳性对照组IL-1β含量降低。低剂量TF-LBM组、中剂量TF-LBM组、高剂量TF-LBM组及阳性对照组IL-6含量均降低。低剂量TF-LBM组及中剂量TF-LBM组TNF-α含量无明显差异,而高剂量TF-LBM组及阳性对照组TNF-α含量降低。与正常老化组相比,模型组小鼠海马组织中IL-1β、IL-6、TNF-α显著增高;与模型组相比,低、中、高剂量TF-LBM组及阳性对照组IL-1β、IL-6、TNF-α含量均降低。结论短管兔耳草总黄酮可以使SAMP8小鼠行为学得到改善,TF-LBM能够降低脑皮层及海马CA1区组织IL-1β、IL-6、TNF-α含量。     

藤黄酸减轻脂多糖诱导的小鼠急性肺损伤

目的探讨藤黄酸(GA)对脂多糖(LPS)所致小鼠急性肺损伤的保护作用及其机制。方法采用尾静脉注射LPS(4 mg/kg)建立小鼠急性肺损伤模型。实验将小鼠随机分为对照组(control组)、模型组(model组)、藤黄酸组(GA组)和藤黄酸预处理组(GA+LPS组),6 h后测定肺湿/干重比值(W/D);检测髓过氧化物酶(MPO)活性;检测肺泡灌洗液(BALF)中蛋白含量和白细胞计数;ELISA检测肺匀浆中白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量。结果模型组小鼠肺W/D、MPO活性、BALF中蛋白含量和白细胞数量均增加,肺组织IL-1β和TNF-α水平升高(均P0.01);藤黄酸预处理可减轻LPS引起的以上指标变化(均P0.05)。结论 GA可减轻LPS诱导的急性肺损伤,其机制可能与降低肺组织IL-1β和TNF-α的含量、抑制中性粒细胞在肺部的聚集和减轻肺部水肿相关。     

TPA致小鼠耳肿胀模型的中性粒细胞聚集及IL-1β、IL-6、TNF-α、IL-17A的表达水平研究

目的从蛋白水平和mRNA水平探讨佛波酯(TPA)诱导的小鼠炎症耳组织中IL-1β、IL-6、TNF-α和IL-17A的表达情况。方法通过HE染色观察TPA致小鼠耳组织的炎症水肿和淋巴细胞浸润,测定髓过氧化物酶(myeloperoxidase,MPO)活性判断中性粒细胞的聚集情况,ELISA法检测IL-1β、IL-6、TNF-α、IL-17A的蛋白含量以及实时荧光定量PCR法检测它们的mRNA水平。结果与正常组相比,模型组小鼠耳组织有明显的炎症水肿和淋巴细胞浸润,中性粒细胞聚集严重,并且该组小鼠耳组织中IL-1β、IL-6、TNF-α的含量和mRNA水平显著地增高,而IL-17A没有明显地变化;阳性药物组与模型组相比,能有效地抑制小鼠耳组织的炎症水肿,淋巴细胞浸润,中性粒细胞聚集以及下调各炎症细胞因子的蛋白含量和mRNA水平。结论 TPA诱导的小鼠耳肿胀严重程度除了与淋巴细胞浸润和中性粒细胞聚集有关外,还与靶组织中显著上调的IL-1β、TNF-α和IL-6蛋白含量和mRNA水平有关。     

Wortmannin对急性肺损伤小鼠肺组织IL-1β和TNF-α表达的影响

目的研究Wortmannin对急性肺损伤模型小鼠肺组织白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)表达的影响。方法 30只昆明小鼠随机分为正常对照组、急性肺损伤组和Wortmannin处理组。采用腹腔注射LPS(10 mg/kg)建立小鼠急性肺损伤模型,对照组腹腔注射同体积的生理盐水,Wortmannin处理组则于造模前2 h腹腔注射Wortmannin(1.4 mg/kg)。LPS注射后6 h处死大鼠,计算肺组织湿/干重(W/D)比值,Western blot方法检测三组小鼠肺组织内IL-1β和TNF-α蛋白的表达变化,RT-PCR方法检测三组小鼠肺组织内IL-1βmRNA和TNF-αmRNA的表达变化。结果急性肺损伤组小鼠肺组织IL-1β和TNF-α蛋白及mRNA表达水平显著上升,显著高于正常对照组(0.05);相比于急性肺损伤组小鼠,Wortmannin处理组小鼠肺组织IL-1β和TNF-α蛋白及mRNA表达水平显著降低(0.05)。结论 Wortmannin能抑制急性肺损伤小鼠肺组织IL-1β和TNF-α表达。     

α7烟碱型乙酰胆碱受体激动剂抑制骨水泥微粒刺激小鼠外周血单核细胞分泌炎性因子

目的探讨α7烟碱型乙酰胆碱受体(α7n AChR)激动剂PNU282987对骨水泥微粒刺激小鼠外周血单核细胞分泌炎性反应因子的影响及其分子机制。方法分离培养小鼠外周血单核细胞,使用聚甲基丙烯酸甲酯(PMMA)微粒刺激后,ELISA检测培养上清液中TNF-α、IL-1β和IL-6的含量;RT-PCR检测细胞TNF-α、IL-1β和IL-6的mRNA表达;Western blot检测p-p65、p65、p-JAK2、JAK2、p-STAT3、STAT3及β-actin的表达;ELISA检测NF-κB DNA结合活力。结果单核细胞经PMMA微粒刺激后,上清液中TNF-α、IL-1β和IL-6的含量明显增高(P0.05);细胞TNF-α、IL-1β和IL-6 mRNA表达明显增高(P0.05);p65、JAK2和STAT3磷酸化明显增强(P0.05);NF-κB DNA结合活力明显增高(P0.05)。不同浓度PNU282987作用后,上清液中TNF-α、IL-1β和IL-6的含量呈浓度依耐性下降(P0.05);细胞TNF-α、IL-1β和IL-6 mRNA表达呈浓度依耐性下降(P0.05);总p65、JAK2和STAT3的表达不变;p-p65、p-JAK2和p-STAT3的表达呈浓度依耐性下降(P0.05);NF-κB DNA结合活力也呈浓度依耐性下降(P0.05)。结论α7n AChR激动剂PNU282987能显著抑制PMMA骨水泥微粒所诱导的小鼠血单核细胞炎性反应因子的分泌。     

Age exacerbates sickness behavior following exposure to a viral mimetic

Poly I:C, a viral mimetic, is a synthetic double-stranded RNA that is known to cause activation of the innate immune system, resulting in the emergence of sickness behaviors in otherwise healthy adult mice. However, the way in which such effects of poly I:C manifest themselves in aged mice are not currently known. We hypothesized that poly I:C administration would lead to burrowing deficits, but that these deficits would be exaggerated in aged subjects (19-months old) compared to young subjects (4-months old) that received the same dose. In order to associate these behavioral decrements with inflammatory factors, we measured mRNA expression of IL-1β and IL-6 in the hippocampus and parietal cortex and peripheral protein expression of IL-6, TNF-α, MCP-1, MIP-1α, and IL-1β in the serum. After exposure to poly I:C, aged subjects demonstrated significant impairments in their burrowing behavior, compared to younger subjects administered the same dose. These behavioral decrements coincided with increased expression of IL-6 among animals exposed to poly I:C and increased expression of IL-1β among aged animals in the hippocampus and cortex. Furthermore, we observed an increase in peripheral poly I:C-induced IL-6, TNF-α, MCP-1, and MIP-1α, but not IL-1β. These results indicate that virus-mediated immune activation in the aging body can lead to increased sickness behavior. Furthermore, these data indicated a possible dissociation between the effects of poly I:C on sickness behaviors in aged mice, with central expression of IL-1β potentially playing a role in age-related impairments.     

The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis

Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.     

The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis

Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.     

Probing the impact of sex steroids and menopause-related sex steroid deprivation on modulation of immune senescence

Immune senescence denotes the general decline in immune system function, characterized by a reduced immune response and an increased inflammatory state. Menopause is a natural change in a women's life, the menopause-related low estrogen levels affecting many body functions, among them the immune system. Numerous human studies with menopausal women and animal models with surgically induced menopause show a clear impact of sex steroids in immune responses. Female superiority in vaccination response and predisposition to infections are eliminated after menopause, while during menopause inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukins-1β, 6, 8 and 13 (IL-1β, IL-6, IL-8, IL-13) and Monocyte Chemoattractant Protein-1 (MCP-1) are increased, implying a molecular connection of sex steroid loss with immune senescence. Moreover, immune cells modify their number and function after the menopausal transition, this offering another explanation for immune senescence. Until now most of the existing studies have concluded that menopause plays an additional role to aging in immune senescence. While it is clear that we are as yet far from thoroughly understanding the molecular pathways connecting sex steroids and menopause with immune senescence, such knowledge is highly likely to enable future targeted interventions in treatment and prevention of age-related diseases in women.     

Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production

The proinflammatory cytokines play a central role in mediating cellular and physiological responses, and levels may reflect immune system effectiveness. In this study, the effect of ageing on the inflammatory response was examined using a novel method to detect production of the proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α), IL-6 and IL-1β. Peripheral blood mononuclear cells (PBMC) obtained from healthy donors of different ages were incubated for 0, 24, 48 and 72 h with or without phorbol 12-myristate 13-acetate (PMA) stimulation. At each time point these cells were permeabilized and incubated with secondary conjugated FITC MoAbs specific for each cytokine. A flow cytometric system was developed to quantify specific intracellular fluorescence in T cells (CD3⁺) and monocytes (CD14⁺). TNF-α, IL-6 and IL-1β production in cell culture supernatants was also measured using ELISAs. In older subjects, flow cytometry detected significant increases in intracellular T cell TNF-α and IL-6 (P < 0.05). IL-1β was not detected in any of the T cell samples. Likewise, the monocytes of older subjects demonstrated increased intracellular levels of all three cytokines, but these increases were not significant (P > 0.05). These changes in intracellular proinflammatory cytokine levels may explain some of the exaggerated inflammatory responses seen in elderly patients.     

小鼠大脑亚硝酸盐暴露与DNA甲基化和组蛋白去乙酰化

目的 观察慢性亚硝酸盐暴露对小鼠大脑皮质炎症损伤的影响及其探讨DNA甲基化和组蛋白去乙酰化等相关机制。方法 选取8周龄健康雄性C57BL/6J小鼠,随机分为对照组（生理盐水）、低剂量亚硝酸盐组（3g/L）和高剂量亚硝酸盐组(6g/L),建立亚硝酸盐暴露模型,收集各组小鼠大脑皮质,利用免疫荧光染色法和Western blotting法分析大脑皮质炎症损伤,组蛋白去乙酰化酶和DNA甲基化相关酶的表达情况。结果 慢性亚硝酸盐暴露后小鼠大脑皮质炎症损伤因子环氧化酶2（COX2）、白细胞介素-1β（IL-1β）、离子钙接头蛋白分子1（Iba1）、c-Fos、IL-6表达量明显多于对照组（P<0.01）,同时高剂量暴露组DNA甲基化相关酶5-甲基胞嘧啶（5-mC）、DNA甲基转移酶1(DNMT1)、DNMT3a、和组蛋白去乙酰化酶1（HDAC1）表达明显低于对照组（P<0.01）且都呈亚硝酸盐剂量依赖性。结论 亚硝酸盐暴露可通过促进细胞免疫炎症对小鼠大脑皮质造成损伤,并且DNA甲基化和组蛋白去乙酰化可能参与了慢性亚硝酸盐暴露过程中的应答过程及其调控机制。     

Cytokines production is altered in mice exposed to airborne suspended matter

The production of IL-2 and IL-4 by thymocytes, spleen and axillary lymph node lymphocytes from female and male mice exposed to airborne suspended matter (ASM) was the scope of our investigations. Cytokines production by activated lymphocytes was determined by the estimation of the percentage of cells positive for intracellular cytokines and by the concentration of both cytokines secreted into the culture medium. Two models of mice exposure to ASM were used: 1/ intraperitoneal injection (acute exposure), and 2/ oral exposure (subacute model). ASM exposure affected both IL-2 and IL-4 production and IL-2R alpha expression on activated lymphoid cells isolated from different lymphoid organs of both female and male mice. The effect was dependent on the route and duration of exposure, ASM dose and the age and sex of mice. A wide panel of changes is discussed. The prolonged exposure to ASM resulted in overproduction of IL-2 in both female and male mice and in overproduction of IL-4 in male mice. Acute exposure to ASM strongly affected IL-2 and IL-4 production, and the effect varied among lymphocytes from different lymphoid organs. Intracellular cytokines expression and the level of secreted cytokines seem to be good tools for the assessment of toxic effects of environmental pollution on the function of the immune system.     

CYTOKINES PRODUCTION IS ALTERED IN MICE EXPOSED TO AIRBORNE SUSPENDED MATTER

ABSTRACT

The production of IL-2 and IL-4 by thymocytes, spleen and axillary lymph node lymphocytes from female and male mice exposed to airborne suspended matter (ASM) was the scope of our investigations. Cytokines production by activated lymphocytes was determined by the estimation of the percentage of cells positive for intracellular cytokines and by the concentration of both cytokines secreted into the culture medium. Two models of mice exposure to ASM were used:1/ intraperitoneal injection (acute exposure), and 2/ oral exposure (subacute model). ASM exposure affected both IL-2 and IL-4 production and IL-2R α expression on activated lymphoid cells isolated from different lymphoid organs of both female and male mice. The effect was dependent on the route and duration of exposure, ASM dose and the age and sex of mice. A wide panel of changes is discussed. The prolonged exposure to ASM resulted in overproduction of IL-2 in both female and male mice and in overproduction of IL-4 in male mice. Acute exposure to ASM strongly affected IL-2 and IL-4 production, and the effect varied among lymphocytes from different lymphoid organs. Intracellular cytokines expression and the level of secreted cytokines seem to be good tools for the assessment of toxic effects of environmental pollution on the function of the immune system.     

Defective immune response and severe skin damage following UVB irradiation in interleukin-6-deficient mice

Interleukin-6 (IL-6), a multifunctional cytokine, is induced in the acute-phase reaction following ultraviolet (UV) irradiation of humans and mice. Using IL-6-deficient (IL-6-/-) mice, we investigated the role of IL-6 in immunosuppression and inflammatory responses caused by UVB (280-320 nm) radiation. The IL-6-/- mice had a defective contact hypersensitivity (CHS) in response to the sensitizers 2,4-dinitrofluorobenzene and oxazolone. The injection of recombinant IL-6 (rIL-6) into these mice resulted in a marked recovery of the CHS. Serum IL-6 was significantly elevated by UV irradiation of wild-type B6 J/129Sv (IL-6+/+) mice but was not detectable in IL-6-/- mice. Interestingly, there was no induction of serum interleukin-10 (IL-10) by UV irradiation of IL-6-/- mice, whereas UV exposure caused a significant increase in serum IL-10 levels in IL-6+/+ mice. Injection of rIL-6 into IL-6-/- mice increased IL-10 to levels similar to those of IL-6+/+ mice. Being different from IL-6+/+ mice, no epidermal proliferation was found at 48 hr in the IL-6-/- mice, but delayed cell proliferation was observed at 72 hr after UV exposure. Immunohistochemical analysis demonstrated that the epidermis was capable of synthesizing IL-6 at 72 hr after UV irradiation of IL-6+/+ mice. In addition, the IL-6-positive cells appeared to be Langerhans' cells, which were detected with dendritic cell-reactive S-100 antibody. The present study strongly suggests that IL-6 may play a crucial role in the alteration of cutaneous immune responses following UV exposure, and provides evidence that IL-6 is a potent inducer of IL-10. Furthermore, IL-6 production induced by UV radiation appears to be an important early signal for repair of UV-caused skin damage.     

Myeloid-Derived Suppressor Cells Protect Mouse Models from Autoimmune Arthritis via Controlling Inflammatory Response

Myeloid-derived suppressor cells (MDSCs) have been reported to participate in immune suppression and autoimmune disorders. However, its role in autoimmune arthritis remains to be determined. We explored whether adoptive transfer of MDSCs in vivo would block joint inflammation and histological damage using collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) models. CD11b⁺ Gr-1⁺ MDSCs were isolated from the single cells from the spleens of CIA mice on day 41 or AIA mice on day 35. MDSCs (2?×?10⁶) were then transferred to AIA and CIA mice via tail vein before arthritis establishment at indicated time points. Phosphate buffered saline (PBS) was injected as control. Arthritis was evaluated by severity score and histology. The levels of TNF-α, IL-6, IL-17 and IL-10 in the serum and joints were detected by enzyme-linked immunosorbent assay (ELISA). The number of Th17 cells and macrophages in draining lymph nodes and joint tissues was assessed by flow cytometric analysis. Adoptive transfer of MDSCs significantly reduced the clinical score of arthritis, alleviated joint inflammation and histological damage both in AIA and CIA models compared with PBS-treated control groups. The levels of TNF-α, IL-6, IL-17, and IL-10 in the serum and joints were down-regulated by transfer of MDSCs. In addition, adoptive transfer of MDSCs significantly reduced the number of Th17 cells and macrophages in draining lymph nodes and joint tissues. Altogether, we demonstrate that adoptive transfer of MDSCs prevented autoimmune arthritis in mouse models of RA through inhibiting Th17 cells and macrophages. These new findings provide insights into the inhibitory functions of MDSCs and MDSCs may be used as a cell-based biotherapy in RA.