The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk

Popa, Călin; Netea, Mihai G.; Riel, P.L.C.M. van; Meer, J.W.M. van der; Stalenhoef, Anton F. H.

doi:10.1194/jlr.r600021-jlr200

Cited by 641 publications

(461 citation statements)

References 89 publications

(137 reference statements)

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“…IL‐1β and IL‐6 are important inflammatory cytokines secreted by macrophages. TNF‐α also is a major mediator in the development of chronic inflammation in diabetes mellitus and rheumatoid arthritis (Popa et al., 2007). Several studies reported suppressive effect of plant extracts on expression of these proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…LPS‐stimulated macrophages mediate the inflammatory response by releasing not only NO but also a variety of proinflammatory cytokines, such as tumor necrosis factor (TNF‐α), interleukin 1β (IL‐1β), and interleukin‐6 (IL‐6), which are related to pathogenesis diseases (Popa, Netea, van Riel, van der Meer, & Stalenhoef, 2007). These cytokines especially TNF‐α could induce insulin resistance in adipocytes (Neels & Olefsky, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Anti‐inflammatory and anti‐insulin resistance activities of aqueous extract from Anoectochilus burmannicus

Budluang

Pitchakarn

Ting

et al. 2016

Food Science & Nutrition

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This study investigated biological activities including antioxidative stress, anti‐inflammation, and anti‐insulin resistance of Anoectochilus burmannicus aqueous extract (ABE). The results showed abilities of ABE to scavenging DPPH and ABTS free radicals in a dose‐dependent manner. Besides, ABE significantly reduced nitric oxide (NO) production in the lipopolysaccharide (LPS)‐treated RAW 264.7 via inhibition of mRNA and protein expressions of nitric oxide synthase (iNOS). The LPS‐induced mRNA expressions of cyclooxygenase‐2 (COX‐2) and interleukin 1β (IL‐1β) were suppressed by ABE. Moreover, ABE exerted anti‐insulin resistance activity as it significantly improved the glucose uptake in tumor necrosis factor (TNF)‐α treated 3T3‐L1 adipocytes. In addition, ABE at the concentration of up to 200 μg/mL was not toxic to human peripheral blood mononuclear cells (PBMCs) and did not induce mutations. Finally, the results of our study suggest the potential use of A. burmannicus as anti‐inflammatory, anti‐insulin resistance agents, or food supplement for prevention of chronic diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti‐inflammatory and anti‐insulin resistance activities of aqueous extract from Anoectochilus burmannicus

Budluang

Pitchakarn

Ting

et al. 2016

Food Science & Nutrition

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“…16 It is well-known that TNF-α is a key proinflammatory cytokine in the pathogenesis of various inflammatory diseases and cancer. 13,17 In addition to directly *Corresponding authors: Huiping Zhou: 1217 East Marshall Street, MSB#533, Richmond, VA 23298, USA. E-mail: hzhou@vcu.edu; Tel:804-828-6817; Fax:804-828-0676., Xiaokun Li: College of Pharmacy, Wenzhou Medical College., E-mail: xiaokunli@163.com.…”

mentioning

confidence: 99%

Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin

Liang

Chen

et al. 2008

Bioorganic & Medicinal Chemistry Letters

131

113

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Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The β-diketone moiety renders curcumin to be rapidly metabolized by aldoketo reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide (LPS)-induced TNF-α and IL-6 synthesis in macrophages.Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Fig. 1] is the major active constituent of turmeric, a yellow compound originally isolated from the plant Curcuma longa L. Tumeric has been widely used for centuries as a dietary spice and pigment. 1 In addition to its unique flavor and color, tumeric has been extensively used in traditional medicine in China and India, particularly as an anti-inflammatory agent. 2 During the last two decades, numerous studies have shown that curcumin has a variety of biological and pharmacological activities such as anti -carcinogen, immuno-modulation, anti-oxidant, antiangiogenesis, and chemo-prevention. 3-9 Recent studies have demonstrated that inflammation is implicated in the pathogenesis of various diseases including cancer, atherosclerosis, diabetes, fatty liver, rheumatoid arthritis, and inflammatory bowel disease. 10-13 Anti-inflammation is the major focus of current drug development. 14 Cytokines are local mediators produced by lymphocytes and macrophages as well as by epithelial and mesenchymal cells. 15 It has been demonstrated that cytokines are involved in a variety of biological processes and play a central role in the development of inflammation and immunity. TNF-α is a multifunctional cytokine produced primarily by activated monocytes/macrophages and plays a critical role in the initiation and continuation of inflammation and immunity. 16 It is well-known that TNF-α is a key proinflammatory cytokine in the pathogenesis of various inflammatory diseases and cancer. 13, 17 In addition to directly *Corresponding authors: Huiping Zhou: 1217 East Marshall Street, MSB#533, Richmond, VA 23298, USA. E-mail: hzhou@vcu.edu; Tel:804-828-6817; Fax:804-828-0676., Xiaokun Li: College of Pharmacy, Wenzhou Medical College., E-mail: xiaokunli@163.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In order to identify the crucial structural motifs leading to anti-inflammatory activity and gain insight into future directions for designing new analogues with better activity, thre...

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“…28 Moreover, decreases in TNFa levels might also protect the arterial wall by lowering plasma triglyceride levels. 23 Our data show that LXRa-modified bone marrow transplantation could lower the IL-6 and TNFa levels in plasma and these changes might be responsible in part for the amelioration of atherogenesis.…”

Section: Discussionmentioning

confidence: 57%

“…Moreover, decrease in TNFa levels might also be protective to the artery by lowing plasma triglyceride levels, as reported previously. 23 …”

Section: Enhanced Expression Of Lxra and Its Target Genes In Macrophagesmentioning

confidence: 99%

Macrophage LXRα gene therapy ameliorates atherosclerosis as well as hypertriglyceridemia in LDLR−/− mice

Biju

Xu³

et al. 2011

Gene Ther

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Liver X receptors (LXRs) are implicated in the regulation of cholesterol homeostasis, inflammatory response and atherogenesis. Administration of LXR agonists inhibits the progress of atherosclerosis, and also increases plasma triglyceride levels, representing an obstacle to their use in treating this disease. The objective of this study was to develop an alternative approach that could overcome this obstacle. Eight-week-old low-density lipoprotein receptor-deficient (LDLR À/À ) mice were transplanted with hematopoietic stem cell (HSC)-enriched bone marrow cells transduced with lentivectors expressing either green fluorescent protein (GFP) (Lenti-SP-GFP, control) or LXRa (Lenti-SP-LXRa) driven by a synthetic macrophage promoter. At 4 weeks post-transplant, the mice were fed with a Western diet for 8 weeks and then killed. Compared with Lenti-SP-GFP mice, the Lenti-SP-LXRa mice had a 30% reduction in atherosclerotic lesions, which was accompanied by increases in levels of macrophage expression of cholesterol efflux genes apolipoprotein E and ATP-binding cassette A1, as well as decreases in plasma inflammatory cytokines interleukin-6 and tumor necrosis factor-a. Intriguingly, a 50% reduction of plasma triglyceride level was also observed. We conclude that HSC-based macrophage LXRa gene therapy ameliorates the development of atherosclerosis along with an unexpected concomitant reduction of plasma triglyceride levels in LDLR À/À mice. These findings highlight the potential value of macrophage LXR expression as an avenue for therapeutic intervention against atherosclerosis.

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The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk

Cited by 641 publications

References 89 publications

Anti‐inflammatory and anti‐insulin resistance activities of aqueous extract from Anoectochilus burmannicus

Anti‐inflammatory and anti‐insulin resistance activities of aqueous extract from Anoectochilus burmannicus

Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin

Macrophage LXRα gene therapy ameliorates atherosclerosis as well as hypertriglyceridemia in LDLR−/− mice

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