Roles of IL-6-gp130 Signaling in Vascular Inflammation

被引:121
作者
Hou, Tieying
Tieu, Brian C.
Ray, Sutapa
Recinos, Adrian, III
Cui, Ruwen
Tilton, Ronald G.
Brasier, Allan R.
机构
[1] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA
[2] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA
[3] Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA
关键词
IL-6; gp-130; angiotensin II; STAT3; vascular inflammation;
D O I
10.2174/157340308785160570
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Interleukin-6 (IL-6) is a well-established, independent indicator of multiple distinct types of cardiovascular disease and all-cause mortality. In this review, we present current understanding of the multiple roles that IL-6 and its signaling pathways through glycoprotein 130 (gp130) play in cardiovascular homeostasis. IL-6 is highly inducible in vascular tissues through the actions of the angiotensin II (Ang II) peptide, where it acts in a paracrine manner to signal through two distinct mechanisms, the first being a classic membrane receptor initiated pathway and the second, a trans-signaling pathway, being able to induce responses even in tissues lacking the IL-6 receptor. Recent advances and new concepts in how its intracellular signaling pathways operate via the Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) are described. IL-6 has diverse actions in multiple cell types of cardiovascular importance, including endothelial cells, monocytes, platelets, hepatocytes and adipocytes. We discuss central roles of IL-6 in endothelial dysfunction, cellular inflammation by affecting monocyte activation/differentiation, cellular cytoprotective functions from reactive oxygen species (ROS) stress, modulation of pro-coagulant state, myocardial growth control, and its implications in metabolic control and insulin resistance. These multiple actions indicate that IL-6 is not merely a passive biomarker, but actively modulates adaptive and pathological responses to cardiovascular stress.
引用
收藏
页码:179 / 192
页数:14
相关论文
共 180 条
  • [1] Akira S, 1996, Curr Opin Hematol, V3, P87
  • [2] IL-6 AND NF-IL6 IN ACUTE-PHASE RESPONSE AND VIRAL-INFECTION
    AKIRA, S
    KISHIMOTO, T
    [J]. IMMUNOLOGICAL REVIEWS, 1992, 127 : 25 - 50
  • [3] Amrani D L, 1990, Blood Coagul Fibrinolysis, V1, P443, DOI 10.1097/00001721-199010000-00013
  • [4] ANDERSON GM, 1993, J BIOL CHEM, V268, P22650
  • [5] ASANO S, 1990, BLOOD, V75, P1602
  • [6] Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro
    Bastard, JP
    Maachi, M
    Van Nhieu, JT
    Jardel, C
    Bruckert, E
    Grimaldi, A
    Robert, JJ
    Capeau, J
    Hainque, B
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (05) : 2084 - 2089
  • [7] Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss
    Bastard, JP
    Jardel, C
    Bruckert, E
    Blondy, P
    Capeau, J
    Laville, M
    Vidal, H
    Hainque, B
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (09) : 3338 - 3342
  • [8] INTERLEUKIN-6 IS REQUIRED IN-VIVO FOR THE REGULATION OF STEM-CELLS AND COMMITTED PROGENITORS OF THE HEMATOPOIETIC SYSTEM
    BERNAD, A
    KOPF, M
    KULBACKI, R
    WEICH, N
    KOEHLER, G
    GUTIERREZRAMOS, JC
    [J]. IMMUNITY, 1994, 1 (09) : 725 - 731
  • [9] Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha
    Bhattacharya, S
    Eckner, R
    Grossman, S
    Oldread, E
    Arany, Z
    DAndrea, A
    Livingston, DM
    [J]. NATURE, 1996, 383 (6598) : 344 - 347
  • [10] Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events
    Biasucci, LM
    Liuzzo, G
    Fantuzzi, G
    Caligiuri, G
    Rebuzzi, AG
    Ginnetti, F
    Dinarello, CA
    Maseri, A
    [J]. CIRCULATION, 1999, 99 (16) : 2079 - 2084