PPARγ-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNFα secretion is not mediated by PTEN regulation

Hong, Guizhu; Davis, Bill; Khatoon, Nachima; Baker, Sharon F.; Brown, John

doi:10.1016/s0006-291x(03)00418-2

Cited by 38 publications

(21 citation statements)

References 27 publications

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“…The fact that TNF␣ production upon PMA stimulation was unaltered is compatible with the notion of specific interference with the TLR-4 pathway, rather than a generalized hyporesponsiveness of the phagocytes. Differential regulation of the 2 pathways has previously been demonstrated with other drugs, such as indomethacin and rosiglitazone (63,64). Although TLR-2 expression on SpA phagocytes was not increased at baseline, it was also significantly down-regulated by infliximab treatment, resulting in lower levels than in healthy controls.…”

Section: De Rycke Et Almentioning

confidence: 77%

Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy

Rycke¹,

Vandooren²,

Kruithof³

et al. 2005

Arthritis & Rheumatism

118

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Results. Expression of TLR-4, but not TLR-2, was increased on PBMCs from patients with SpA, whereas both TLRs were increased in RA patients. TLR expression was particularly increased on the CD163؉ macrophage subset. Infliximab reduced TLR-2 and TLR-4 expression on monocytes of SpA and RA patients, leading to lower levels than in controls and to impaired TNF␣ production upon LPS stimulation. In inflamed synovium, the expression of both TLRs and of CD163 was significantly higher in patients with SpA than in those with RA or OA. Paralleling the systemic effect, TLRs in synovium were down-regulated following treatment with infliximab as well as etanercept, indicating a class effect of TNF␣ blockers.Conclusion. Inflammation in SpA is characterized by increased TLR-2 and TLR-4 expression, which is sharply reduced by TNF␣ blockade. These findings suggest a potential role of innate immunity-mediated inflammation in SpA and provide an additional clue regarding the mechanism of action as well as the potential side effects of TNF␣ blockade.

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Section: De Rycke Et Almentioning

confidence: 77%

Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy

Rycke¹,

Vandooren²,

Kruithof³

et al. 2005

Arthritis & Rheumatism

118

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“…Additionally, pharmacological affinity studies have previously shown that of the 4 TZD's, Rosi has the highest affinity for PPARg, followed by Pioglitazone > Troglitazone > Ciglitazone. 29,30 Previously, PPARg agonists, in particular Rosi, have been shown to correlate with PTEN expression in MCF-7 breast cancer cells, 18 macrophages, 18 monocytes, 44 bronchoalveolar lavage cells 45 and AsPC-1 pancreatic cancer cells. 46 We show here that stimulation of MCF-7 cells with 30 lM Rosi results in a~1.5-fold increase in PTEN.…”

Section: Discussionmentioning

confidence: 99%

Increased PTEN expression due to transcriptional activation of PPARγ by Lovastatin and Rosiglitazone

Teresi

Shaiu

Chen

et al. 2006

Intl Journal of Cancer

107

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Germline mutations in the tumor suppressor gene PTEN (protein phosphatase and tensin homolog located on chromosome ten) predispose to heritable breast cancer. The transcription factor PPARc has also been implicated as a tumor suppressor pertinent to a range of neoplasias, including breast cancer. A putative PPARc binding site in the PTEN promoter indicates that PPARc may regulate PTEN expression. We show here that the PPARc agonist Rosiglitazone, along with Lovastatin, induce PTEN in a dose-and time-dependent manner. Lovastatin-or Rosiglitazoneinduced PTEN expression was accompanied by a decrease in phosphorylated-AKT and phosphorylated-MAPK and an increase in G1 arrest. We demonstrate that the mechanism of Lovastatin-and Rosiglitazone-associated PTEN expression was a result of an increase in PTEN mRNA, suggesting that this increase was transcriptionally-mediated. Compound-66, an inactive form of Rosiglitazone, which is incapable of activating PPARc, was unable to elicit the same response as Rosiglitazone, signifying that the Rosiglitazone response is PPARc-mediated. To support this, we show, using reporter assays including dominant-negative constructs of PPARc, that both Lovastatin and Rosiglitazone specifically mediate PPARc activation. Additionally, we demonstrated that cells lacking PTEN or PPARc were unable to induce PTEN mediated cellular events in the presence of Lovastatin or Rosiglitazone. These data are the first to demonstrate that Lovastatin can signal through PPARc and directly demonstrate that PPARc can upregulate PTEN at the transcriptional level. Since PTEN is constitutively active, our data indicates it may be worthwhile to examine Rosiglitazone and Lovastatin stimulation as mechanisms to increase PTEN expression for therapeutic and preventative strategies including cancer, diabetes mellitus and cardiovascular disease. ' 2006 Wiley-Liss, Inc.

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“…PI-3,4,5-trisphosphate levels are negatively controlled by several phosphatases, including the ubiquitously expressed PTEN (which hydrolyzes PI-3,4,5-trisphosphate to PI-4,5-bisphosphate) and SHIP2 [which hydrolyzes PI-3,4,5-trisphosphate to PI-3,4-bisphosphate (56) Previous studies (14,23,29,38,46,63) have shown that thiazolidinediones increase the expression of PTEN and downregulate PI3K activity. In our study, Pio increased myocardial PTEN expression.…”

Section: Pten and Ship2mentioning

confidence: 99%

Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions

Lin

Atar

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

102

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We assessed 1) whether pretreatment before ischemia with pioglitazone (Pio) limits infarct size (IS) and whether this protective effect is due to nitric oxide synthase (NOS) and/or prostaglandin production, as has been shown for atorvastatin (ATV); and 2) whether Pio and ATV have synergistic effects on myocardial protection. Sprague-Dawley rats received oral ATV (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), Pio (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), their combination (Pio ϩ ATV), or water alone for 3 days. Additional rats received Pio (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 3 days and intravenous SC-58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min before ischemia. Rats underwent 30 min of myocardial ischemia and 4 h of reperfusion, or hearts were harvested for analysis. IS in the Pio and in the ATV groups was significantly smaller than in the sham-treated group. IS in the Pio ϩ ATV group was smaller than in all other groups (P Ͻ 0.001 vs. each group). The protective effect of Pio was abrogated by SC-58125 but not by SC-560. Pio, ATV, and Pio ϩ ATV increased the expression and activity of cytosolic phospholipase A 2 (cPLA2) and COX-2. ATV increased phosphorylatedAkt, phosphorylated-endothelial NOS (P-eNOS), inducible NOS, and COX-2 levels. In contrast, Pio caused an insignificant increase in myocardial levels of phosphorylated-Akt but did not change P-eNOS and iNOS expression. In conclusion, the IS-limiting effects of Pio and ATV involve COX-2. However, the upstream steps differ. ATV induced eNOS phosphorylation and iNOS, cPLA 2, and COX-2 expression, whereas Pio induced mainly the expression and activity of cPLA 2. The effects of Pio and ATV were additive. infarct size; thiazolidinediones; statins; cyclooxygenase-2; cytosolic phospholipase A2; nitric oxide synthase; protein kinase Akt; phosphatase and tensin homologue deleted on chromosome 10, anti-Src homology 2-containing inositol phosphatase-2

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PPARγ-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNFα secretion is not mediated by PTEN regulation

Cited by 38 publications

References 27 publications

Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy

Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy

Increased PTEN expression due to transcriptional activation of PPARγ by Lovastatin and Rosiglitazone

Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions

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