Elevated Cyclic AMP Inhibits NF-κB-mediated Transcription in Human Monocytic Cells and Endothelial Cells

Ollivier, Véronique; Parry, Graham; Cobb, Ronald R.; Prost, Dominique de; Mackman, Nigel

doi:10.1074/jbc.271.34.20828

Cited by 334 publications

(234 citation statements)

References 55 publications

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“…Known NF-B-dependent genes include IL-12, TNF-␣, IL-6, MCP-1, KC, and IL-1␤ (12,27,41,42). Elevation of intracellular cAMP by cAMP-elevating agents decreased LPS-induced NF-B function as shown in this study and in several other studies (37,(43)(44)(45) and this effect was partially attenuated by Rp-8-Br-cAMPS, suggesting that PGI 2 analogs may suppress NF-B function by activating the cAMP-signaling pathway. Although the mechanism of NF-B inhibition by cAMP remains to be investigated, it is possible that elevated levels of cAMP result in more activated CREB.…”

Section: Discussionsupporting

confidence: 69%

Prostaglandin I2 Analogs Inhibit Proinflammatory Cytokine Production and T Cell Stimulatory Function of Dendritic Cells

Zhou

Hashimoto

Goleniewska

et al. 2007

The Journal of Immunology

153

145

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Signaling through the PGI2 receptor (IP) has been shown to inhibit inflammatory responses in mouse models of respiratory syncytial viral infection and OVA-induced allergic responses. However, little is known about the cell types that mediate the anti-inflammatory function of PGI2. In this study, we determined that PGI2 analogs modulate dendritic cell (DC) cytokine production, maturation, and function. We report that PGI2 analogs (iloprost, cicaprost, treprostinil) differentially modulate the response of murine bone marrow-derived DC (BMDC) to LPS in an IP-dependent manner. The PGI2 analogs decreased BMDC production of proinflammatory cytokines (IL-12, TNF-α, IL-1α, IL-6) and chemokines (MIP-1α, MCP-1) and increased the production of the anti-inflammatory cytokine IL-10 by BMDCs. The modulatory effect was associated with IP-dependent up-regulation of intracellular cAMP and down-regulation of NF-κB activity. Iloprost and cicaprost also suppressed LPS-induced expression of CD86, CD40, and MHC class II molecules by BMDCs and inhibited the ability of BMDCs to stimulate Ag-specific CD4 T cell proliferation and production of IL-5 and IL-13. These findings suggest that PGI2 signaling through the IP may exert anti-inflammatory effects by acting on DC.

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Section: Discussionsupporting

confidence: 69%

Prostaglandin I2 Analogs Inhibit Proinflammatory Cytokine Production and T Cell Stimulatory Function of Dendritic Cells

Zhou

Hashimoto

Goleniewska

et al. 2007

The Journal of Immunology

153

145

View full text Add to dashboard Cite

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“…Transcription of the tnf-α gene is suppressed by the NF-κB p50 subunit which constitutively binds the IκB element in the promoter region (Kuprash et al, 1995, Jimenez et al, 2001, Takahashi et al, 2002, Foey et al, 2003. PKA phosphorylation of Ser337 on the NF-κB p50 subunit increases its binding and repression of transcription of IκB-containing gene promoter of the tnf-α gene (Ollivier et al, 1996, Baer et al, 1998, Hou et al, 2003. How the cAMP pathway regulates IL-1β expression is an active area of investigation.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the cAMP signaling pathway after traumatic brain injury

Atkins

Oliva

Alonso

et al. 2007

Experimental Neurology

137

151

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Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream target, protein kinase A, from 15 min to 48 hr after moderate FPI. To determine if preventing hydrolysis of cAMP by administration of a phosphodiesterase (PDE) IV inhibitor would improve outcome after TBI, we treated animals intraperitoneally with rolipram (0.3 or 3.0 mg/kg) 30 min prior to TBI, and then once per day for three days. Rolipram treatment restored cAMP to sham levels and significantly reduced cortical contusion volume and improved neuronal cell survival in the parietal cortex and CA3 region of the hippocampus. Traumatic axonal injury, characterized by β-amyloid precursor protein deposits in the external capsule, was also significantly reduced in rolipramtreated animals. Furthermore, levels of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were significantly decreased with rolipram treatment. These results demonstrate that the cAMP-PKA signaling cascade is downregulated after TBI, and that treatment with a PDE IV inhibitor improves histopathological outcome and decreases inflammation after TBI. Keywordscamp; Fluid-percussion; Inflammation; Interleukin-1β; PKA; Phosphodiesterase; Rolipram; TNF-α; Traumatic brain injury; TBI Traumatic brain injury (TBI) is a prevalent, debilitating health problem, occurring in 1.4 million people each year and disabling 5 million people in the United States (Langlois et al., 2004). The subsequent progressive injury after brain trauma develops from hours to days after the initiating insult, providing an accessible time window for pharmacological therapies. Despite Address correspondence to: W. Dalton Dietrich, Scientific Director, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, P.O. Box 016960, (R-48), Miami, FL 33101, E-mail: ddietrich@miami.edu, Phone: 305-243-2297, Fax: 305-243-3207. 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. Brain trauma results in contusion formation, neuronal apoptosis, and axonal tract damage. These pathologies are worsened by the inflammatory cascade set into motion by the initial injury (Morganti-Kossmann et al., 2002. Two pro-i...

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“…Since NF-k B binding sites are identified in the PAI-1 promotor region [43], AGE probably enhanced the transcription of PAI-1 gene through the NF-k B-mediated pathway. Agonists that increase intracellular cyclic AMP concentrations inhibit the NF-k B-mediated gene transcription in HUVEC [44]. Accordingly, AGE-induced PAI-1 mRNA upregulation would be enhanced by the decrease in cyclic AMP.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells

et al. 1998

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Accelerated atherosclerosis and microvascular complications are perhaps the leading cause of coronary heart disease, blindness and renal failure which are common complications in patients with prolonged diabetes [1±3]. Plasminogen activator inhibitor-1 (PAI-1) is an important fast-acting serine protease inhibitor that attenuates fibrinolysis [4]. Epidemiological studies have demonstrated that reduced fibrinolytic activity because of elevated plasma PAI-1 is an important factor in various thrombotic diseases such as deep vein thrombosis, ischaemic heart disease [5±8] and diabetic vascular complications [9±10]. In addition to the attenuated fibrinolytic activity, hypercoagulability and platelet hyperaggregation are also prevalent in diabetic patients, contributing to microthrombus formation in diabetic micro-and macroangiopathies [11]. The molecular mechanisms underlying these thrombogenic abnormalities, however, are not fully understood. Diabetologia (1998) Summary Several thrombogenic abnormalities are associated with diabetes. To investigate the underlying molecular mechanisms, we examined the effects of advanced glycation endproducts (AGE), non-enzymatically glycated protein derivatives, on the production of prostacyclin (PGI 2 ), an anti-thrombogenic prostanoid, and of plasminogen activator inhibitor-1 (PAI-1), a fast-acting serine protease inhibitor of fibrinolysis, in human microvascular endothelial cells (EC). Firstly, AGE-bovine serum albumin (BSA) but not non-glycated BSA, was found to considerably decrease the production of PGI 2 to about two-thirds of the control value. Secondly, quantitative reverse transcription-polymerase chain reaction showed that AGE-BSA increased the EC levels of mRNA coding for PAI-1, this being associated with a concomitant increase in the immunoreactive PAI-1 contents and the anti-fibrinolytic activity. Thirdly, the effects of AGE on PGI 2 and PAI-1 syntheses in EC were found to be mediated by a receptor for AGE (RAGE) because antisense DNA against RAGE mRNA could reverse the AGE effects. Further, it was found that AGE decreased the intracellular cyclic AMP concentrations in EC and that cyclic AMP agonists such as dibutyryl cyclic AMP, forskolin and PGI 2 analogue reduced the AGE-stimulated PAI-1 production, suggesting the involvement of cyclic AMP in the AGE-signalling pathway. The results thus suggest that AGE have the ability to cause platelet aggregation and fibrin stabilization, resulting in a predisposition to thrombogenesis and thereby contributing to the development and progression of diabetic vascular complications.[ Diabetologia (1998

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Elevated Cyclic AMP Inhibits NF-κB-mediated Transcription in Human Monocytic Cells and Endothelial Cells

Cited by 334 publications

References 55 publications

Prostaglandin I2 Analogs Inhibit Proinflammatory Cytokine Production and T Cell Stimulatory Function of Dendritic Cells

Prostaglandin I2 Analogs Inhibit Proinflammatory Cytokine Production and T Cell Stimulatory Function of Dendritic Cells

Modulation of the cAMP signaling pathway after traumatic brain injury

Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells

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