Versatile functions for IL-6 in metabolism and cancer

被引:336
作者
Mauer, Jan [1 ]
Denson, Jesse L. [1 ]
Bruening, Jens C. [1 ]
机构
[1] Max Planck Inst Metab Res, Cologne, Germany
关键词
interleukin-6; metabolism; cancer; inflammation; C-REACTIVE PROTEIN; INDUCED INSULIN-RESISTANCE; NECROSIS-FACTOR-ALPHA; BROWN ADIPOSE-TISSUE; ALTERNATIVE ACTIVATION; SKELETAL-MUSCLE; MESSENGER-RNA; IN-VIVO; CARBOHYDRATE-METABOLISM; MACROPHAGE ACTIVATION;
D O I
10.1016/j.it.2014.12.008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Owing to its abundance in inflammatory settings, interleukin IL-6 is frequently viewed as a proinflammatory cytokine, with functions that parallel those of tumor necrosis factor (TNF) and IL-1 beta in the context of inflammation. However, accumulating evidence points to a broader role for IL-6 in a variety of (patho)physiological conditions, including functions related to the resolution of inflammation. We review recent findings on the complex biological functions governed by IL-6 signaling, focusing on its role in inflammation-associated cancer and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We propose that the anti-inflammatory functions of IL-6 may extend to multiple settings and cell types, and suggest that these dimensions should be incorporated in therapeutic approaches to these diseases. Finally, we outline important areas of inquiry towards understanding this pleiotropic cytokine.
引用
收藏
页码:92 / 101
页数:10
相关论文
共 119 条
[1]   Inhibition of IL-6 and IL-10 signaling and Stat activation by inflammatory and stress pathways [J].
Ahmed, ST ;
Ivashkiv, LB .
JOURNAL OF IMMUNOLOGY, 2000, 165 (09) :5227-5237
[2]   MOLECULAR-CLONING OF APRF, A NOVEL IFN-STIMULATED GENE FACTOR-3 P91-RELATED TRANSCRIPTION FACTOR INVOLVED IN THE GP130-MEDIATED SIGNALING PATHWAY [J].
AKIRA, S ;
NISHIO, Y ;
INOUE, M ;
WANG, XJ ;
WEI, S ;
MATSUSAKA, T ;
YOSHIDA, K ;
SUDO, T ;
NARUTO, M ;
KISHIMOTO, T .
CELL, 1994, 77 (01) :63-71
[3]   IKK-β links inflammation to obesity-induced insulin resistance [J].
Arkan, MC ;
Hevener, AL ;
Greten, FR ;
Maeda, S ;
Li, ZW ;
Long, JM ;
Wynshaw-Boris, A ;
Poli, G ;
Olefsky, J ;
Karin, M .
NATURE MEDICINE, 2005, 11 (02) :191-198
[4]   Adipocyte Inflammation Is Essential for Healthy Adipose Tissue Expansion and Remodeling [J].
Asterholm, Ingrid Wernstedt ;
Tao, Caroline ;
Morley, Thomas S. ;
Wang, Qiong A. ;
Delgado-Lopez, Fernando ;
Wang, Zhao V. ;
Scherer, Philipp E. .
CELL METABOLISM, 2014, 20 (01) :103-118
[5]   Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation:: Evidence in Crohn disease and experimental colitis in vivo [J].
Atreya, R ;
Mudter, J ;
Finotto, S ;
Müllberg, J ;
Jostock, T ;
Wirtz, S ;
Schütz, M ;
Bartsch, B ;
Holtmann, M ;
Becker, C ;
Strand, D ;
Czaja, J ;
Schlaak, JF ;
Lehr, HA ;
Autschbach, F ;
Schürmann, G ;
Nishimoto, N ;
Yoshizaki, K ;
Ito, H ;
Kishimoto, T ;
Galle, PR ;
Rose-John, S ;
Neurath, MF .
NATURE MEDICINE, 2000, 6 (05) :583-588
[6]   Adiponectin Enhances Insulin Sensitivity by Increasing Hepatic IRS-2 Expression via a Macrophage-Derived IL-6-Dependent Pathway [J].
Awazawa, Motoharu ;
Ueki, Kohjiro ;
Inabe, Kazunori ;
Yamauchi, Toshimasa ;
Kubota, Naoto ;
Kaneko, Kazuma ;
Kobayashi, Masatoshi ;
Iwane, Aya ;
Sasako, Takayoshi ;
Okazaki, Yukiko ;
Ohsugi, Mitsuru ;
Takamoto, Iseki ;
Yamashita, Satoshi ;
Asahara, Hiroshi ;
Akira, Shizuo ;
Kasuga, Masato ;
Kadowaki, Takashi .
CELL METABOLISM, 2011, 13 (04) :401-412
[7]   Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro [J].
Bastard, JP ;
Maachi, M ;
Van Nhieu, JT ;
Jardel, C ;
Bruckert, E ;
Grimaldi, A ;
Robert, JJ ;
Capeau, J ;
Hainque, B .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (05) :2084-2089
[8]   Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss [J].
Bastard, JP ;
Jardel, C ;
Bruckert, E ;
Blondy, P ;
Capeau, J ;
Laville, M ;
Vidal, H ;
Hainque, B .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (09) :3338-3342
[9]   TGF-β suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling [J].
Becker, C ;
Fantini, MC ;
Schramm, C ;
Lehr, HA ;
Wirtz, S ;
Nikolaev, A ;
Burg, J ;
Strand, S ;
Kiesslich, R ;
Huber, S ;
Ito, H ;
Nishimoto, N ;
Yoshizaki, K ;
Nishimoto, N ;
Galle, PR ;
Blessing, M ;
Rose-John, S ;
Neurath, MF .
IMMUNITY, 2004, 21 (04) :491-501
[10]   Orchestration of Metabolism by Macrophages [J].
Biswas, Subhra K. ;
Mantovani, Alberto .
CELL METABOLISM, 2012, 15 (04) :432-437