Modulation of Monocyte Chemokine Production and Nuclear Factor Kappa B Activity by Oxidants

Lee, Janet; Kahlon, Summerpal S.; Culbreth, Rachel; Cooper, John A.

doi:10.1089/107999099313613

Cited by 18 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, a short burst of NO augments the activation of NF-B in LPS or TNF-␣stimulated cells [176,177], and other studies show that longer duration of NO exposure led to inhibition and served as a negative-feedback signal [178 -180]. Other observations with ROS show that low levels of H 2 O 2 can similarly enhance NF-B activity [181,182], and higher H 2 O 2 (Ͼ100 M) inhibited its activity [178 -180]. These redox-mediated inhibitory reactions involve critical cysteine thiolates necessary for DNA binding [183][184][185].…”

Section: No and Proinflammatory Genesmentioning

confidence: 99%

Nitric oxide and redox mechanisms in the immune response

Wink

Hines

Cheng

et al. 2011

Journal of Leukocyte Biology

643

510

View full text Add to dashboard Cite

The role of redox molecules, such as NO and ROS, as key mediators of immunity has recently garnered renewed interest and appreciation. To regulate immune responses, these species trigger the eradication of pathogens on the one hand and modulate immunosuppression during tissue-restoration and wound-healing processes on the other. In the acidic environment of the phagosome, a variety of RNS and ROS is produced, thereby providing a cauldron of redox chemistry, which is the first line in fighting infection. Interestingly, fluctuations in the levels of these same reactive intermediates orchestrate other phases of the immune response. NO activates specific signal transduction pathways in tumor cells, endothelial cells, and monocytes in a concentration-dependent manner. As ROS can react directly with NO-forming RNS, NO bioavailability and therefore, NO response(s) are changed. The NO/ROS balance is also important during Th1 to Th2 transition. In this review, we discuss the chemistry of NO and ROS in the context of antipathogen activity and immune regulation and also discuss similarities and differences between murine and human production of these intermediates.

show abstract

Section: No and Proinflammatory Genesmentioning

confidence: 99%

Nitric oxide and redox mechanisms in the immune response

Wink

Hines

Cheng

et al. 2011

Journal of Leukocyte Biology

643

510

View full text Add to dashboard Cite

show abstract

“…Studies have shown that in the setting of fatty liver, the severity of oxidative injury depends upon the degree of unsaturation of cellular lipids (60,61). High levels of unsaturation amplify oxidative insults, leading to enhanced lipid peroxidation and downstream consequences such as chemokine production (62)(63)(64). In our experiments, the substantial LPS-induced rise in TBARS that occurred in Mttp ⌬/⌬ mice relative to control mice is likely due to their disproportionate stores of linoleic acid, an essential polyunsaturated fatty acid.…”

Section: Mttpmentioning

confidence: 99%

Blocking the Secretion of Hepatic Very Low Density Lipoproteins Renders the Liver More Susceptible to Toxin-induced Injury

Björkegren¹,

Beigneux²,

Bergö³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Recently, we generated mice lacking microsomal triglyceride transfer protein (MTP) in the liver (Mttp ⌬/⌬ ) and demonstrated that very low density lipoprotein secretion from hepatocytes was almost completely blocked. The blockade in lipoprotein production was accompanied by mild to moderate hepatic steatosis, but the mice appeared healthy. Although hepatic MTP deficiency appeared to be innocuous, we hypothesized that a blockade in very low density lipoprotein secretion and the accompanying steatosis might increase the sensitivity of Mttp ⌬/⌬ livers to additional hepatic insults. To address this issue, we compared the susceptibility of Mttp Microsomal triglyceride transfer protein (MTP)1 is critical for the assembly and secretion of apolipoprotein (apo) B-containing lipoproteins, both in the intestine and in the liver (1, 2). A genetic absence of MTP causes abetalipoproteinemia, a disease characterized by intestinal fat malabsorption, a virtual absence of chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins in the plasma, and strikingly low plasma levels of triglycerides and cholesterol. The fact that a deficiency in MTP reduces the plasma levels of atherogenic lipoproteins has attracted the attention of the pharmaceutical industry. Many companies have established MTP programs, with the goal of identifying MTP inhibitors suitable for treating humans with hyperlipidemias (3, 4). Thus far, however, the efficacy and safety of these compounds in humans has not been documented.To investigate the role of MTP in lipoprotein assembly and secretion, we inactivated the MTP gene (Mttp) in mice (5). Heterozygous knockout mice (Mttp ϩ/Ϫ ) manifested slightly reduced levels of lipoprotein secretion, reduced levels of apoB100-containing lipoproteins in the plasma, and slightly increased levels of neutral lipids (triglycerides and cholesterol esters) in the liver. Homozygous knockout mice (Mttp Ϫ/Ϫ ) died during embryonic development. Subsequently, we used Cre/LoxP recombination techniques to produce mice lacking Mttp expression in the liver but not in the intestine (6). Those mice, designated Mttp ⌬/⌬ mice, exhibited strikingly reduced plasma levels of apoB100, sizable reductions in the plasma levels of cholesterol and triglycerides, and mild to moderate steatosis with increased levels of neutral lipids in the liver. The Mttp ⌬/⌬ mice were healthy and grew normally; their plasma transaminase levels were normal, and their livers were free of inflammatory infiltrates (6).The fact that it was possible to eliminate hepatic Mttp expression in a mammalian model without noticeable side effects supported the concept that it might be possible to develop MTP inhibitors to treat hyperlipidemias. Also encouraging were studies by Wetterau et al. (7) that showed that MTP inhibitors could reduce plasma lipoprotein levels in low density lipoprotein receptor-deficient rabbits without causing elevated transaminases or histologic evidence of liver inflammation.In this study, we further investigated the notion that it mig...

show abstract

“…17,18 Similarly, generation of ROIs with xanthine/ xanthine oxidase induced IL-8 and MCP-1 production from monocytes, but not U937 cells, and this induction is associated with increased NF-B DNA binding. 20 Thus the potential for a role of ROIs in induction of MCP-1 in venular endothelium was considered.…”

mentioning

confidence: 99%

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Lakshminarayanan

Lewallen

Frangogiannis

et al. 2001

The American Journal of Pathology

102

View full text Add to dashboard Cite

Monocyte chemotactic protein (MCP)-1 is a member of the CC chemokine family and serves as a chemotactic factor for the recruitment of monocytes and subpopulations of T cells during inflammation. 1 It is induced by the proinflammatory cytokines interleukin (IL)-1␤ and tumor necrosis factor (TNF)-␣, as well as phorbol esters, which regulate its induction at the transcriptional level through the cooperative interaction of the transcription factors AP-1 and nuclear factor (NF)-B. 2-4 Specifically, in endothelial cells, IL-1␤, TNF-␣, and phorbol esters mediate human MCP-1 gene expression through the cooperative interaction of the NF-B binding site at Ϫ90 bp (relative to the start site) and the AP-1 binding site at Ϫ68 bp. 2,3 Early reperfusion of the ischemic myocardium is a key clinical intervention after myocardial infarction and is attended by a robust inflammatory reaction involving both neutrophils and mononuclear cells. 5,6 It has been shown that late reperfusion, when myocardial salvage is no longer possible, improves myocardial repair and obviates infarct expansion.

show abstract

Modulation of Monocyte Chemokine Production and Nuclear Factor Kappa B Activity by Oxidants

Cited by 18 publications

References 33 publications

Nitric oxide and redox mechanisms in the immune response

Nitric oxide and redox mechanisms in the immune response

Blocking the Secretion of Hepatic Very Low Density Lipoproteins Renders the Liver More Susceptible to Toxin-induced Injury

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Contact Info

Product

Resources

About