Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 <i>in vitro</i>

Deng, Jingjing; James, Christian H; Patel, Lisa; Smith, Alberto; Burnand, K. G.; Rahmoune, Hassan; Lamb, Jonathan R.; Davis, Bill

doi:10.1042/cs20080058

Cited by 22 publications

(23 citation statements)

References 29 publications

(42 reference statements)

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“…TRIB3 has been revealed to be upregulated in atherosclerotic unstable plaque (20). Studies demonstrated that TRIB3 is upregulated by oxidized LDL (21) and mediates human monocyte-derived macrophage apoptosis (22).…”

Section: Discussionmentioning

confidence: 99%

Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE−/−/LDL Receptor−/− Mice

et al. 2012

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Insulin resistance triggers the developments of diabetes mellitus and atherosclerosis. Tribbles homolog 3 (TRIB3) is involved in insulin resistance. We aimed to investigate whether TRIB3 is implicated in diabetic atherosclerosis. Sixty 3-week-old apolipoprotein E (ApoE−/−)/LDR receptor (LDLR−/−) mice were randomly divided into chow and diabetes groups. Diabetes was induced by a high-fat and high-sugar diet combined with low-dose streptozotocin. Mice in both groups were randomly divided into vehicle and TRIB3-silencing groups. After transfection, all mice were killed to evaluate the effects of TRIB3 on atherosclerosis. Silence of TRIB3 markedly decreased insulin resistance (P = 0.039) and glucose (P = 0.019), regardless of diabetes. Ultrasonography-measured parameters were similar in both groups, with and without silence of TRIB3. However, silence of TRIB3 decreased the aortic atherosclerotic burden (P = 1 × 10−13). Further study showed that in brachiocephalic lesions, fibrous cap thickness, cap-to-core ratio, collagen content, and the number of smooth muscle cells were significantly increased (P < 0.01 for all) by silence of TRIB3, whereas lipid and macrophage contents remained unaltered, with the vulnerability index significantly reduced. Moreover, the numbers of apoptotic cells and macrophages in brachiocephalic lesions were both significantly decreased (P < 0.01 for both). Macrophage migration was decreased (P = 4 × 10−4) by knocking down TRIB3, whereas adhesion and phagocytosis were increased (P < 0.05 for both). Silence of TRIB3 would diminish atherosclerotic burden and increase the plaque stability in diabetic mice.

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Section: Discussionmentioning

confidence: 99%

Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE−/−/LDL Receptor−/− Mice

et al. 2012

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“…They are involved in various cell functions and act as regulators of different signalling pathways, MAPK and NF-KB signal transduction for instance [3,45,46]. TRIB expression is modulated by different stimuli [47,48] as an example, TRIB-2 expression can be stimulated in response to TLR ligands [8]. Consequently any alteration in the expression of TRIB can affect their function and the signalling pathway which they control.…”

Section: Resultsmentioning

confidence: 98%

Tribbles role in reproduction

Basatvat

Carter

Kiss-Tóth

et al. 2015

Biochemical Society Transactions

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Tribbles (TRIB) proteins, a family of evolutionary conserved psuedokinase proteins, modulate various signalling pathways within the cell. The regulatory roles of TRIB make them an important part of a number of biological processes ranging from cell proliferation to metabolism, immunity, inflammation and carcinogenesis. Innate immune system plays a pivotal role during the regulation of reproductive processes that allows successful creation of an offspring. Its involvement initiates from fertilization of the oocyte by spermatozoon and lasts throughout early embryonic development, pregnancy and labour. Therefore, there is a close cooperation between the reproductive system and the innate immune system. Evidence from our lab has demonstrated that improper activation of the innate immune system can reduce embryo implantation, thus leading to infertility. Therefore, control mechanisms regulating the innate immune system function can be critical for successful reproductive events.

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“…First, a potential role for TRB3 in atherogenesis was established by studies demonstrating that TRB3 was expressed in unstable regions of human carotid plaques 10 and that silencing of TRB3 suppressed atherosclerosis and stabilized plaques in diabetic ApoE -/-/LDL receptor -/-mice. 11 Second, we have shown that TRB3 induces insulin resistance in cultured muscle and adipose cells and mediates glucoseinduced insulin resistance in diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…They were found to be expressed in unstable regions of human carotid plaques, and the silencing of TRB3 suppressed atherosclerosis and stabilized plaques in diabetic ApoE -/-/ LDL receptor -/-mice. 10,11 There are many events that lead to the formation of an atherosclerotic lesion, but the initial lesion is the formation of macrophage foam cell. These are cells that coalesce to produce fatty streaks in the endothelium of large arteries.…”

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confidence: 99%

Tribbles Homolog 3 Promotes Foam Cell Formation Associated with Decreased Proinflammatory Cytokine Production in Macrophages: Evidence for Reciprocal Regulation of Cholesterol Uptake and Inflammation

Steverson

Tian

et al. 2016

Metabolic Syndrome and Related Disorders

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Background: Insulin resistance is central in the pathophysiology of cardiometabolic disease; however, common mechanisms that explain the parallel development of both type 2 diabetes and atherosclerosis have not been elucidated. We have previously shown that tribbles homolog 3 (TRB3) can exert a chronic pathophysiological role in promoting insulin resistance and also has an acute physiological role to alternatively regulate glucose uptake in fat and muscle during short-term fasting and nutrient excess. Since TRB3 is expressed in human atherosclerotic plaques, we explored its role in foam cell formation to assess its potential contribution to atherogenesis. Methods: We have used human THP-1 monocytes, which transition to lipid-laden macrophage foam cells when exposed to oxidized low-density lipoprotein (ox-LDL). Results: We first observed that TRB3 was upregulated by more than twofold (P < 0.01) within 24 hr of treatment with ox-LDL. To determine whether TRB3 actively participated in foam cell formation, we overexpressed TRB3 in THP-1 monocytes and found that this led to a 1.5-fold increase in cholesterol accumulation after 48 hr (P < 0.01), compared with controls. At the same time, TRB3 overexpression suppressed inflammation in macrophages as evidenced by reduced expression and secretion of tumor necrosis factor alpha (TNF-a) and interleukin-1 beta (IL-1b) (both P < 0.01). Conclusions: (1) TRB3 is upregulated in macrophages upon treatment with ox-LDL; (2) TRB3 promotes lipid accumulation and suppresses cytokine expression; and (3) inflammation and foam cell formation can be reciprocally regulated, and TRB3 orients the macrophage to assume a more primary role for lipid accumulation while maintaining a secondary role as an inflammatory immune cell.

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Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro

Cited by 22 publications

References 29 publications

Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE−/−/LDL Receptor−/− Mice

Silence of TRIB3 Suppresses Atherosclerosis and Stabilizes Plaques in Diabetic ApoE−/−/LDL Receptor−/− Mice

Tribbles role in reproduction

Tribbles Homolog 3 Promotes Foam Cell Formation Associated with Decreased Proinflammatory Cytokine Production in Macrophages: Evidence for Reciprocal Regulation of Cholesterol Uptake and Inflammation

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