Chinese Journal of Tissue Engineering Research ›› 2017, Vol. 21 ›› Issue (16): 2612-2618.doi: 10.3969/j.issn.2095-4344.2017.16.026
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Liu Yang1, 2, Yang Rui1, 3, Yuan Hong-bin3, Shi Jian-gang2, Yao Ding-kang4
Revised:
2017-04-13
Online:
2017-06-08
Published:
2017-07-06
Contact:
Yao Ding-kang, M.D., Professor, Department of Internal Medicine, Shanghai Changzheng Hospital, Shanghai 200003, China
About author:
Liu Yang, Studying for doctorate, Physician, School of Graduate, the Second Military Medical University, Shanghai 200433, China; Second Department of Spine, Shanghai Changzheng Hospital, Shanghai 200003, China
Yang Rui, Studying for doctorate, Physician, School of Graduate, the Second Military Medical University, Shanghai 200433, China; Department of Anesthesiology, Shanghai Changzheng Hospital, Shanghai 200003, China
Liu Yang and Yang Rui contributed equally to this work.
Supported by:
the National Natural Science Foundation of China, No. 81271351 and 81371253; the Innovation Foundation for the Undergraduates in the Second Military Medical University, No. ZD2016010, MS2016058, FH2016171 and FH2016180
CLC Number:
Liu Yang, Yang Rui, Yuan Hong-bin, Shi Jian-gang, Yao Ding-kang. Role of adipokines in the occurrence and regulation of autoimmune diseases[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(16): 2612-2618.
2.1 脂肪组织和炎症自身免疫 脂肪组织包含脂肪细胞和一部分T细胞及髓系细胞。较瘦的状态下,脂肪组织更倾向抗炎状态,此时,Th2细胞占T细胞群主导,调节性T细胞、调节性B细胞和恒定自然杀伤细胞群数量足够大并有效抑制炎症。肥胖倾向导致免疫细胞数量增加。自身免疫疾病是一种进行性发展的炎症反应,而慢性肥胖则为自身免疫疾病的进展提供了预置的环境。因此,有报导将肥胖和某些自身免疫性疾病的高风险或疾病进展活跃联系在一起,这些疾病包括类风湿性关节炎、系统性红斑狼疮、多发性硬化、克罗恩病、溃疡性结肠炎和银屑病[9-10]。除改变脂肪组织中的免疫细胞构成外,肥胖也会导致脂肪因子表达改变。这些因子主要包括在脂肪组织中分泌的一系列细胞因子和趋化因子,如白细胞介素1β、白细胞介素6、CCL2、肿瘤坏死因子α等。 2.2 瘦素 瘦素是首个通过在肥胖小鼠(ob/ob小鼠)中原位克隆而被发现的脂肪因子,是一种相对分子质量为16 000的未被糖基化的多肽激素,被归类为长链螺旋细胞因子家族的一员,该家族还包括白细胞介素6、白细胞介素11、白细胞介素12和白血病抑制因子。瘦素作用于广泛表达在中枢神经系统、心血管系统和免疫系统的OB-Rb长型异构体受体,能够通过提升饱腹感和提高能量消耗,在调节体质量上发挥重要作用[11]。瘦素缺乏小鼠会发生肥胖,且循环中瘦素水平与脂肪组织多少相关[9,12]。这些小鼠同样为免疫缺陷小鼠,这说明瘦素在调节免疫应答中的作用[13]。瘦素作为促炎介质在固有免疫和获得性免疫应答中发挥作用[14]。在固有免疫中,瘦素参与促炎分子的产生和免疫信号级联反应,与中性粒细胞动员、巨噬细胞活化和吞噬作用、NK细胞活化和树突状细胞存活相关[15]。在单核细胞中可激活单核细胞增殖,刺激他们产生白三烯B4、二十烷酸和肿瘤坏死因子α、白细胞介素6和白细胞介素12等促炎因子。在中性粒细胞中可增强细胞趋化作用和释放氧自由基,并在获得性免疫过程中,瘦素通过激活表达瘦素受体的T细胞增殖,使T细胞向促炎的Th1表型转化,同时作为负向调节因子作用于抑制自身免疫的调节性T细胞[9]。另一方面,瘦素能抵消其他激素的作用,如诱发饥饿的促胃液素[16]。校正体质量指数后,女性的瘦素水平比男性要高,这提示性别因素在某些疾病中,包括多发性硬化、系统性红斑狼疮等主要影响女性的疾病中起重要作用[17]。 瘦素的表达增高与多种自身免疫疾病相关。在动物实验中,瘦素缺乏小鼠其干扰素γ表达被抑制,白细胞介素10表达增加,故抗原诱导的关节炎程度较轻[18]。然而,Hultgren等[19]报道在诱导关节炎小鼠模型中,发现瘦素水平显著下降,但在外源性补充瘦素后,这些补充的瘦素既不能维持瘦素的水平,也不能恢复小鼠在疾病过程中丢失的体质量,但却可以显著降低关节炎的严重程度,这种作用可能与血清中白细胞介素6的水平降低有关。Prete等[20]收集了31个类风湿关节炎病例和18个健康对照,发现在类风湿性关节炎患者中,血清瘦素的水平升高,且血清与关节滑液中瘦素含量的比值与关节侵蚀的程度相关。Chung等[21]比较了37例系统性红斑狼疮患者和80例健康对照,发现在系统性红斑狼疮和对照组间,血清瘦素的水平显著升高,但与疾病活动并无关系。在动物实验中,瘦素对系统性红斑狼疮的影响则较大。Fujita等[22]构建了MRL/Mp-Faslpr小鼠,这种小鼠会发展出类似系统性红斑狼疮的表现,首先发现瘦素在系统性红斑狼疮小鼠模型中表达增高,而后将其与瘦素缺乏小鼠杂交,发现瘦素缺乏的小鼠中系统性红斑狼疮的表现较轻,且CD3+CD4−CD8−B220+ T细胞(lpr细胞)的数量降低。瘦素缺乏也在其它实验室诱导的炎症性疾病的小鼠模型中起保护作用,包括结肠炎、1型糖尿病、肝炎和实验性自身免疫性脑脊髓炎,究其原因,瘦素在这些模型中调节T细胞的应答,降低模型对疾病的易感性[23]。Emamgholipour等[24]在规模为391例,包括191例多发性硬化患者的研究中发现,多发性硬化患者的血清瘦素水平会显著上升,且与肿瘤坏死因子α和白细胞介素1β等免疫介质水平正相关,且在进展型多发性硬化患者中,瘦素和肿瘤坏死因子α、白细胞介素1β的水平会更高。此外,在白塞氏病、银屑病和溃疡性结肠炎急性期会出现瘦素表达升高,但在强直性脊柱炎、抗中性粒细胞胞浆抗体相关性血管炎中表达降低[25]。总的来说,这些研究证明,在不同的自身免疫性疾病中,瘦素确实在调节疾病发生或对疾病应答反应中有一定的潜在作用,当然,这种作用还需进一步实验研究加以确证。 2.3 脂联素 脂联素属于胶原超家族,与Ⅷ型胶原、 X型胶原和补体因子C1q同源,包含多种亚型,是在血清中水平最高的脂肪因子。与大多数脂肪因子不同的是,脂联素在血浆中的水平在肥胖的个体中会下降,随体质量的下降而上升,提示其与其他脂肪因子的作用并不相同。共有3种受体介导脂联素通路:脂联素受体1主要在骨骼肌细胞中表达;脂联素受体2在肝脏中表达较多;T-钙粘蛋白,主要表达于心血管系统。脂联素和瘦素都是胰岛素敏感的脂肪因子。除了增强胰岛素的敏感性,脂联素还可以降低肝脏糖原生成,促进胰岛素基因表达、骨骼肌和脂肪细胞的糖摄取,并进一步在肝脏和骨骼肌中增加游离脂肪酸的氧化代谢。 瘦素具有促炎症反应的活性,而与瘦素相反,脂联素一致被认为是一种抗炎脂肪因子,特别是它对血管壁的保护作用。的确,脂联素在内皮细胞中通过抑制肿瘤坏死因子α诱导黏附分子,如血管细胞黏附分子1、内皮细胞-白细胞黏附分子1和细胞间黏附分子1,这可以减弱单核细胞对内皮细胞的黏附作用。脂联素可以抑制巨噬细胞的成熟、增殖和细胞吞噬作用,并且降低炎症刺激后巨噬细胞肿瘤坏死因子α和干扰素γ的分泌。此外脂联素还促进巨噬细胞吞噬凋亡细胞的作用,避免凋亡细胞诱发炎症或免疫系统的功能异常。脂联素可降低肿瘤坏死因子α和白细胞介素6的分泌与活性,并诱导单核细胞、巨噬细胞和树突状细胞抗炎因子如白细胞介素10和白细胞介素1受体拮抗物的产出。脂联素亦可以升高调节性T细胞的数量。相反的是脂联素会促进树突状细胞的成熟和活化。肿瘤坏死因子α和白细胞介素6是脂联素分泌的潜在抑制剂,提示脂联素和促炎细胞因子间可能存在负反馈调节。脂联素的其他抗炎作用还包括抑制白细胞介素2诱导的NK细胞杀细胞作用。在获得性免疫中,脂联素能降低肿瘤坏死因子α水平与T淋巴细胞和B淋巴细胞的活化和增殖[26]。有趣的是,多个研究最近证明脂联素起到促炎作用,能够增高促炎递质的表达和活性,包括基质金属蛋白酶3、基质金属蛋白酶9、白细胞介素6、CCL2和白细胞介素8[27]。在自身免疫性炎症的状态下血清脂联素水平会升高。但导致这种矛盾发生的原因尚不清楚,可能与不同亚型的脂联素有关,高分子量的脂联素主要起抗炎作用,低分子量的脂联素起促炎反应。 脂联素功能的分歧因自身免疫疾病类型不同而存在差异。Chen等[28]观察了197例类风湿性关节炎患者,类风湿性关节炎患者血清和关节滑液中脂联素水平均升高,且与影像学损伤、疾病活动、红细胞沉降率和类风湿因子正相关,可以在非肥胖症的类风湿性关节炎患者中有效反应关节损伤的状态。Klein-Wieringa等[29]对类风湿性关节炎患者随访达4年时间,并监测患者关节的影像学和脂联素的改变,发现脂联素水平可有效预测类风湿性关节炎的疾病进展。脂联素水平在强直性脊柱炎、1型糖尿病和溃疡性结肠炎中也有升高,具有作为这些疾病标志物的潜能[30-33]。在系统性红斑狼疮的狼疮小鼠模型中,脂联素随肾损伤的进展而降低,起到自身免疫负向调节因子的作用[34]。相反,有研究证实,在系统性红斑狼疮患者中血清脂联素水平升高,并与疾病活动有一定相关性[35]。在多发性硬化中,脂联素水平在动物模型和患者血清中均降低,与白细胞活化水平增高和调节性T细胞数量降低有关[36]。银屑病与其相似,血清脂联素基础水平低于健康对照,但在治疗组中脂联素的含量显著升高[25,37]。干燥综合征小鼠模型中,唾液腺中脂联素水平降低[38]。显然,脂联素对炎症自身免疫有着不可忽视的影响,若能证实其在疾病中的确切作用,则有助于揭开其双向作用的机制。 2.4 抵抗素 抵抗素最初与小鼠脂肪细胞、胰岛素抵抗和肥胖相关,而人抵抗素主要产自骨髓来源的单核细胞,部分来自脂肪细胞[39]。人体内抵抗素的水平与其他一些黏附分子如细胞间黏附分子1和炎症反应的标志物如Ⅱ型肿瘤坏死因子受体和脂蛋白相关磷脂酶A2平行。尽管在鼠和人中抵抗素存在差异,但抵抗素与炎症反应高度相关性却被广泛认可。有研究证实,内毒素脂多糖可以在人和小鼠的原代巨噬细胞中诱导抵抗素的高表达,与其他促炎因子分泌的调节位于同一级联反应中。抵抗素可与人白细胞表面的toll样受体4结合,导致白细胞介素12、白细胞介素6、和白细胞介素1β等促炎细胞因子产生,反过来这些细胞因子又会刺激抵抗素表达,这些细胞因子与抵抗素间的相互诱导是通过核因子κB通路完成的[39],形成正向反馈调节。在体外应用抵抗素处理脂肪细胞、外周血单核细胞和肝星状细胞会导致促炎反应[40-41]。类风湿患者中的血浆和滑液中抵抗素的水平升高,且循环中抵抗素水平增高与炎症标志物和类风湿性关节炎关节损伤相关,关节腔内注射抵抗素可诱发关节炎,诱导白细胞在滑膜组织的浸润、滑膜的增厚和关节翳形成。Gonzalez-Gay等[42]发现,在类风湿性关节炎患者使用英夫利昔单抗,即肿瘤坏死因子α拮抗剂后,类风湿性关节炎患者中抵抗素的表达会显著降低。尽管对系统性红斑狼疮的抵抗素研究结果不同,但抵抗素可在预示炎症活动和系统性红斑狼疮相关肾病的活动程度中起到一定的作用[21,43]。抵抗素水平在复发缓解型多发性硬化、强直性脊柱炎、银屑病患者中升高,血清抵抗素水平也与糖尿病炎症、干燥综合征和炎症性肠病相关[25,39,44-45]。这些研究证明抵抗素可作为一般炎症状态和自身免疫的有效标志物,其在介导自身免疫炎症中可能起到特殊的作用。 2.5 内脂素 内脏脂肪素简称内脂素,除炎症递质之外的作用研究较少,只有少量证据说明它有胰岛素样特性[46]。内脂素最初在肝、骨骼肌和骨髓中被发现,由于他能增强前B细胞群形成,称为前B细胞群增强因子[47]。内脂素在急性肺损伤和脓毒症的模型中表达上调。但是之后的研究发现内脂素由脂肪细胞大量生产,受糖皮质激素、肿瘤坏死因子、白细胞介素6和生长激素的调控,同时影响促炎(白细胞介素6、肿瘤坏死因子α、白细胞介素1β)和抗炎(白细胞介素10、白细胞介素1受体拮抗剂)细胞因子生成[48-49]。内脂素不仅在白色脂肪组织中表达,它也可以由内毒素刺激过的中性粒细胞表达,预防caspase 3和caspase 8介导的细胞凋亡。内脂素同时作为化学引诱物作用于单核细胞和淋巴细胞,促进单核细胞共刺激分子的表达[50]。在类风湿性关节炎中,循环和滑膜成纤维细胞中内脂素水平均增高,且与疾病严重程度和关节破坏程度相关。在对促炎症刺激反应时,内脂素表达增加,通过自分泌形式引起细胞因子表达并增强白细胞介素6产生[51]。除此之外,抑制内脂素功能会降低关节炎小鼠模型的疾病严重程度[52]。内脂素在复发缓解型多发性硬化、银屑病、溃疡性结肠炎、克罗恩病患者中表达也会增加[24-25,53]。其中,在炎症性肠病中,内脂素被发现可诱导趋化反应并促进白细胞介素β、肿瘤坏死因子、白细胞介素6和CD14+单核细胞共刺激分子的表达,并通过p38和MAP激酶—ERK激酶MEK通路,增强它们在促进淋巴细胞增殖中的作用。在类风湿性关节炎患者中内脂素水平和功能状况与疾病程度相关,可作为炎症和疾病进展的标志物,在其它检测到内脂素增高的患者中,内脂素是否具有同样的标志物作用还有待进一步证实。 2.6 趋化素 趋化素能调节脂肪细胞的产生,与体质量指数增高和代谢综合征强相关[54]。尽管趋化素和脂肪组织由较强关联,但趋化素在自身免疫炎症中的作用的研究比其作为脂肪因子更早。趋化素最早在类风湿性关节炎患者的滑液中被分离出,它与疾病活动程度正相 关[55] 。血清趋化素水平对促炎细胞因子肿瘤坏死因子α、白细胞介素6、和C-反应蛋白有参考性[56-57]。在系统性红斑狼疮、类风湿性关节炎、特别是银屑病中,趋化素招募并活化浆细胞样树突状细胞,对髓系细胞的动员起到了重要作用,是早期损伤形成的标志物[58]。在溃疡性结肠炎和克罗恩病中,趋化素的水平也会升高,并通过抑制抗炎巨噬细胞影响炎症过程[32,59]。多发性硬化患者中,趋化素与肥胖有关,这提示肥胖在增强多发性硬化的炎症反应中起到一定作用[60]。在多种自身免疫性疾病中都已经证实了趋化素的作用,而趋化素的表达又与肥胖高度相关,故接下来的研究中,趋化素可作为一个中间桥梁,用来研究肥胖和自身免疫性疾病的关系。 2.7 其他脂肪因子 如在前文所说,有超过50种脂肪因子被报道,综述中只涉及到了其中少数几个与自身免疫相关的因子。除了这些已经被深入研究的代表,其他的脂肪因子成员也在被研究其与自身免疫疾病的关系。脂质运载蛋白(lipocalin-2,NGAL)在人和小鼠中的脂肪组织中均有分泌,功能是调节产热,通过形成异二聚体从而激活并保护基质金属蛋白酶9[61]。脂质运载蛋白在类风湿性关节炎患者的滑膜成纤维细胞中比在骨关节炎换这种表达量增高,而且是狼疮性肾炎的候选标志物[62]。在类风湿性关节炎中,脂质运载蛋白的表达是由粒细胞-巨噬细胞集落刺激因子诱导的,来抵消表皮细胞生长因子和成纤维细胞生长因子2对软骨细胞增殖的正向调控,可能加剧关节的损伤[63]。 在肥胖的状态下,铁调素(hepcidin)在脂肪细胞中高表达。铁调素的作用是维持铁稳态,它的表达与炎症紧密相关。在炎症的状况下,铁调素的水平升高会导致巨噬细胞的铁内流,限制红细胞生成并导致系统性的贫血,包含慢性炎症导致的贫血。在溃疡性结肠炎小鼠模型中,促炎因子(如白细胞介素6等)激活STAT3,使铁调素水平升高[64]。此外,铁调素在狼疮性肾炎中表达升高,并且在类风湿性关节炎患者中与贫血和炎症相关,它还与动脉硬化的程度平行[65]。 网膜素(即内凝集素)的相对分子质量为40 000,被认为是一种部位特异性的脂肪因子,在网膜脂肪组织中分泌,在人血浆中含量丰富。有研究证实,网膜素基因的表达和在循环中的浓度与炎症状态和肥胖相关。网膜素可通过促进AMP依赖的蛋白激酶/内皮型一氧化氮合酶信号通路抑制JNK的激活,是一种抗炎因子[66]。通过同时抑制细胞外调节蛋白激酶/核因子κB和p38/JNK信号通路,网膜素可以抑制单核细胞的黏附[67]。同时,它还可以识别致病的乳糖呋喃残基,促进噬菌作用清除病原,参与到固有免疫中。最近有报道中提到,在克罗恩病(非溃疡性结肠炎)、银屑病、银屑病关节炎中,网膜素的表达下降,提示网膜素可能是一种在自身免疫疾病中发挥作用的候选因子[68]。 C1q/肿瘤坏死因子α相关蛋白与脂联素具有明显的序列同源性,其中的几种被认为是脂肪因子,发挥抑制Toll样受体4诱导的炎症反应和升高白细胞介素10水平等抗炎作用。缺乏C1q/肿瘤坏死因子α相关蛋白3的小鼠更容易发生胶原诱导性关节炎,证明C1q/肿瘤坏死因子α相关蛋白3在关节炎发生中发挥了重要作用[69]。因为C1q/肿瘤坏死因子α相关蛋白家族刚刚被认为是免疫调节因子,其他对C1q/肿瘤坏死因子α相关蛋白蛋白在自身免疫中作用的研究尚未被报道。这些研究较少的脂肪因子提示脂肪因子当前研究的两方面特点。第一,尽管脂肪因子和炎症间的作用已经被深入研究,但脂肪因子在免疫调节中作用的研究才刚刚开始。随着这个领域研究的开展,脂肪因子和炎症性疾病间新的联系被不断发现,脂肪因子在这个过程中未知的作用也不断被揭示。第二,继续深入研究它们在自身免疫中的作用。15年前没有人会想到脂肪组织分泌的蛋白会影响自身免疫疾病的发生,现在则一定会考虑与脂肪组织、代谢等领域相关的免疫调节信号通路可能在自身免疫炎症中发挥重要的作用。"
[1] Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005;115(5):911-919; quiz 920.[2] Mohamed-Ali V, Goodrick S, Rawesh A, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997;82(12) 4196-4200.[3] Chimen M, Yates CM, McGettrick HM, et al. Monocyte Subsets Coregulate Inflammatory Responses by Integrated Signaling through TNF and IL-6 at the Endothelial Cell Interface. J Immunol. 2017;198(7):2834-2843. [4] Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014;220(2):T47-59. [5] Smolen JS, Steiner G, Aringer M. Anti-cytokine therapy in systemic lupus erythematosus. Lupus. 2005;14(3): 189-191.[6] Shimizu S, Kouzaki H, Kato T, et al. HMGB1-TLR4 signaling contributes to the secretion of interleukin 6 and interleukin 8 by nasal epithelial cells. Am J Rhinol Allergy. 2016;30(3):167-172. [7] Davidson A, Diamond B. Autoimmune diseases. N Engl J Med. 2001;345(5):340-350.[8] Ermann J, Fathman CG. Autoimmune diseases: genes, bugs and failed regulation. Nat Immunol. 2001;2(9):759-761.[9] Versini M, Jeandel PY, Rosenthal E, et al. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13(9):981-1000.[10] Harpsøe MC, Basit S, Andersson M, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol. 2014;43(3): 843-855. [11] Ahima RS, Prabakaran D, Mantzoros C, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382 (6588):250-252.[12] Jéquier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002;967:379-388.[13] Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol. 2000;68(4): 437-446.[14] Lago F, Dieguez C, Gómez-Reino J, et al. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol. 2007;3(12):716-724.[15] Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol. 2005;174(6):3137-3142.[16] Kalra SP, Ueno N, Kalra PS. Stimulation of appetite by ghrelin is regulated by leptin restraint: peripheral and central sites of action. J Nutr. 2005;135(5):1331-1335.[17] Matarese G, Sanna V, Di Giacomo A, et al. Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males. Eur J Immunol. 2001;31(5):1324-1332.[18] Busso N, So A, Chobaz-Péclat V, et al. Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol. 2002; 168(2):875-882.[19] Hultgren OH, Tarkowski A. Leptin in septic arthritis: decreased levels during infection and amelioration of disease activity upon its administration. Arthritis Res. 2001;3(6):389-394.[20] Del Prete A, Salvi V, Sozzani S. Adipokines as potential biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014; 2014:425068. [21] Chung CP, Long AG, Solus JF, et al. Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis. Lupus. 2009; 18(9):799-806.[22] Fujita Y, Fujii T, Mimori T, et al. Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice. J Immunol. 2014;192(3):979-984. [23] Matarese G, Di Giacomo A, Sanna V, et al. Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol. 2001;166(10):5909-5916.[24] Emamgholipour S, Eshaghi SM, Hossein-nezhad A, et al. Adipocytokine profile, cytokine levels and foxp3 expression in multiple sclerosis: a possible link to susceptibility and clinical course of disease. PLoS One. 2013;8(10):e76555. [25] Toussirot E, Aubin F, Dumoulin G. Relationships between Adipose Tissue and Psoriasis, with or without Arthritis. Front Immunol. 2014;5:368.[26] Ohashi K, Parker JL, Ouchi N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010;285(9):6153-6160.[27] Gómez R, Scotece M, Conde J, et al. Adiponectin and leptin increase IL-8 production in human chondrocytes. Ann Rheum Dis. 2011;70(11):2052-2054.[28] Chen X, Lu J, Bao J, et al. Adiponectin: a biomarker for rheumatoid arthritis? Cytokine Growth Factor Rev. 2013;24(1): 83-89.[29] Klein-Wieringa IR, van der Linden MP, Knevel R, et al. Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthritis. Arthritis Rheum. 2011;63(9):2567-2574.[30] Derdemezis CS, Filippatos TD, Voulgari PV, et al. Leptin and adiponectin levels in patients with ankylosing spondylitis. The effect of infliximab treatment. Clin Exp Rheumatol. 2010;28(6): 880-883. [31] Karmiris K, Koutroubakis IE, Xidakis C, et al. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(2):100-105.[32] Weigert J, Obermeier F, Neumeier M, et al. Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease. Inflamm Bowel Dis. 2010;16(4):630-637. [33] Imagawa A, Funahashi T, Nakamura T, et al. Elevated serum concentration of adipose-derived factor, adiponectin, in patients with type 1 diabetes. Diabetes Care. 2002;25(9): 1665-1666.[34] Parker J, Menn-Josephy H, Laskow B, et al. Modulation of lupus phenotype by adiponectin deficiency in autoimmune mouse models. J Clin Immunol. 201;31(2):167-173. [35] Al M, Ng L, Tyrrell P, et al. Adipokines as novel biomarkers in paediatric systemic lupus erythematosus. Rheumatology (Oxford). 2009;48(5):497-501. [36] Piccio L, Cantoni C, Henderson JG, et al. Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis. Eur J Immunol. 2013;43(8):2089-2100. [37] Li RC, Krishnamoorthy P, DerOhannessian S, et al. Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors. Clin Exp Dermatol. 2014;39(1):19-24.[38] Su YC, Xiang RL, Zhang Y, et al. Decreased submandibular adiponectin is involved in the progression of autoimmune sialoadenitis in non-obese diabetic mice. Oral Dis. 2014; 20(8):744-755. [39] Jamaluddin MS, Weakley SM, Yao Q, et al. Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol. 2012;165(3):622-632. [40] Fu Y, Luo L, Luo N, et al. Proinflammatory cytokine production and insulin sensitivity regulated by overexpression of resistin in 3T3-L1 adipocytes. Nutr Metab (Lond). 2006;3:28.[41] Bertolani C, Sancho-Bru P, Failli P, et al. Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. Am J Pathol. 2006;169(6):2042-2053.[42] Gonzalez-Gay MA, Garcia-Unzueta MT, Gonzalez-Juanatey C, et al. Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2008;26(2):311-316.[43] Hutcheson J, Ye Y, Han J, et al. Resistin as a potential marker of renal disease in lupus nephritis. Clin Exp Immunol. 2015; 179(3):435-443. [44] Kraszula L, Jasińska A, Eusebio M, et al. Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis. Neurol Neurochir Pol. 2012;46(1):22-28.[45] Kocabas H, Kocabas V, Buyukbas S, et al. The serum levels of resistin in ankylosing spondylitis patients: a pilot study. Rheumatol Int. 2012;32(3):699-702. [46] Revollo JR, Körner A, Mills KF, et al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007;6(5):363-375.[47] Samal B, Sun Y, Stearns G, et al. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol. 1994;14(2):1431-1437.[48] Friebe D, Neef M, Kratzsch J, et al. Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Diabetologia. 2011;54(5):1200-1211.[49] Catalán V, Gómez-Ambrosi J, Rodríguez A, et al. Association of increased visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity. Nutr Metab Cardiovasc Dis. 2011;21(4):245-253. [50] Stofkova A. Resistin and visfatin: regulators of insulin sensitivity, inflammation and immunity. Endocr Regul. 2010; 44(1):25-36.[51] Matsui H, Tsutsumi A, Sugihara M, et al. Visfatin (pre-B cell colony-enhancing factor) gene expression in patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67(4):571-572.[52] Busso N, Karababa M, Nobile M, et al. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD. PLoS One. 2008;3(5):e2267. [53] Waluga M, Hartleb M, Boryczka G, et al. Serum adipokines in inflammatory bowel disease. World J Gastroenterol. 2014; 20(22):6912-6917. [54] Jialal I, Devaraj S, Kaur H, et al. Increased chemerin and decreased omentin-1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol Metab. 2013; 98(3):E514-517. [55] Ha YJ, Kang EJ, Song JS, et al. Plasma chemerin levels in rheumatoid arthritis are correlated with disease activity rather than obesity. Joint Bone Spine. 2014;81(2):189-190. [56] Weigert J, Neumeier M, Wanninger J, et al. Systemic chemerin is related to inflammation rather than obesity in type 2 diabetes. Clin Endocrinol (Oxf). 2010;72(3):342-348. [57] Lehrke M, Becker A, Greif M, et al. Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol. 2009;161(2):339-344.[58] Albanesi C, Scarponi C, Bosisio D, et al. Immune functions and recruitment of plasmacytoid dendritic cells in psoriasis. Autoimmunity. 2010;43(3):215-219.[59] Lin Y, Yang X, Yue W, et al. Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization. Cell Mol Immunol. 2014;11(4):355-366. [60] Tomalka-Kochanowska J, Baranowska B, Wolinska-Witort E, et al. Plasma chemerin levels in patients with multiple sclerosis. Neuro Endocrinol Lett. 2014;35(3):218-223.[61] Guo H, Jin D, Zhang Y, et al. Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice. Diabetes. 2010;59(6):1376-1385. [62] Gupta K, Shukla M, Cowland JB, et al. Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9. Arthritis Rheum. 2007;56(10):3326-3335.[63] Shao S, Cao T, Jin L, et al. Increased Lipocalin-2 Contributes to the Pathogenesis of Psoriasis by Modulating Neutrophil Chemotaxis and Cytokine Secretion. J Invest Dermatol. 2016;136(7):1418-1428. [64] Shanmugam NK, Trebicka E, Fu LL, et al. Intestinal inflammation modulates expression of the iron-regulating hormone hepcidin depending on erythropoietic activity and the commensal microbiota. J Immunol. 2014;193(3): 1398-1407. [65] Mohammed MF, Belal D, Bakry S, et al. A study of hepcidin and monocyte chemoattractant protein-1 in Egyptian females with systemic lupus erythematosus. J Clin Lab Anal. 2014; 28(4):306-309. [66] Yamawaki H, Kuramoto J, Kameshima S, et al. Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun. 2011;408(2):339-343.[67] Kazama K, Usui T, Okada M, et al. Omentin plays an anti-inflammatory role through inhibition of TNF-α-induced superoxide production in vascular smooth muscle cells. Eur J Pharmacol. 2012;686(1-3):116-123.[68] Lu Y, Zhou L, Liu L, et al. Serum omentin-1 as a disease activity marker for Crohn's disease. Dis Markers. 2014;2014: 162517. [69] Schäffler A, Buechler C. CTRP family: linking immunity to metabolism. Trends Endocrinol Metab. 2012;23(4):194-204. |
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