The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.
The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.
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DOI：
10.1371/journal.pone.0094188
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
McKay DM
中科院分区：
文献类型：
--
作者：
Fernando MR;Reyes JL;Iannuzzi J;Leung G;McKay DM
巨噬细胞是重要的先天免疫细胞，与两种不同的表型相关：一种是促炎（或经典激活）亚群，具有原型巨噬细胞功能，如炎症细胞因子产生和杀菌活性；另一种是抗炎（或替代激活（AAM））亚群，与伤口愈合和组织修复过程相关。在本研究中，我们检测了白细胞介素-6对人和小鼠巨噬细胞极化的影响。结果表明，尽管白细胞介素-6通常与促炎功能相关，并参与许多炎症疾病的发病机制/病理生理，但它可以通过增加标记物的表达来增强AAMs的极化：精氨酸酶-1、Ym1和CD206；这种作用需要AAM分化细胞因子IL-4和IL-13。AAM与IL-6共同处理导致IL-10的自发释放，抑制lps诱导的一氧化氮的产生，并通过激活CD4+ T细胞抑制细胞因子的产生-免疫调节特性在“亲本”IL-4+ il -13诱导的AAM中未观察到。IL-6的作用部分依赖于IL4Rα链的上调，而不依赖于自分泌IL-10。在IFNγ存在的情况下，IL-6促进IL-1β和TNFα的产生，这表明这种细胞因子可以增强巨噬细胞的表型。这一发现可以解释IL-6的多养性，它与炎症情况下疾病的延续和增强有关，但对于其他情况下炎症的消退和充分的伤口愈合也是必要的。因此，在体内调节或抑制IL-6的免疫疗法中，可能需要考虑IL-6在促进AAM中的潜在益处，以及它的抗炎和伤口愈合能力。
Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM)) subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells – immunoregulatory features not observed in the ‘parent’ IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT)-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its’ anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.
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影响因子：
9.3
作者：
Guerrero AR;Uchida K;Nakajima H;Watanabe S;Nakamura M;Johnson WE;Baba H
通讯作者：
Baba H
影响因子：
3.7
作者：
Antignano, Frann;Hamilton, Melisa;Krystal, Gerald
通讯作者：
Krystal, Gerald
DOI：
10.1164/rccm.200509-1518oc
发表时间：
2006-04-01
影响因子：
24.7
作者：
Prasse, A;Pechkovsky, DV;Zissel, G
通讯作者：
Zissel, G
影响因子：
4.4
作者：
Kurowska-Stolarska, Mariola;Stolarski, Bartosz;Liew, Foo Y.
通讯作者：
Liew, Foo Y.
影响因子：
7.3
作者：
Qualls JE;Neale G;Smith AM;Koo MS;DeFreitas AA;Zhang H;Kaplan G;Watowich SS;Murray PJ
通讯作者：
Murray PJ