PPAR-γ agonists inhibit production of monocyte inflammatory cytokines

Jiang, Chengyu; Ting, Adrian T.; Seed, Brian

doi:10.1038/34184

Cited by 2,321 publications

(2,035 citation statements)

References 26 publications

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“…Jiang et al 10 and Jiang et al 18 confirmed that PPARγ did express in human monocytes, and showed that PPARγ agonists (15d-PGJ2 and synthetic PPARγ ligands) could markedly upregulate PPARγ and processing of inflammatory cytokines in activated human macrophages at agonist concentrations similar to those found to be effective for the promotion of adipogenesis. Some genes are negatively regulated by PPARγ including inducible nitric oxide synthase, IL-1, IL-6, TNF-α, 10 and several other genes induced by interferon-γ (IFN-γ).…”

Section: Discussionmentioning

confidence: 88%

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Downregulation of Peroxisome Proliferator‐activated Receptor‐γ Expression in Hypertensive Atrial Fibrillation

Chen¹,

Bing²,

He³

et al. 2009

Clinical Cardiology

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Background: Numerous evidence has suggested that either hypertension or atrial fibrillation (AF) is associated with systemic inflammation. Peroxisome proliferator-activated receptor-γ (PPARγ) has been proved to have anti-inflammatory effects and is implicated as a molecular pathway involved in many cardiovascular diseases, such as hypertension. The correlation between PPARγ inflammation and AF is still unknown. Methods: Using a case-control study design, 57 patients with hypertensive AF (persistent AF: 32, paroxysmal AF: 25) were included into the study groups. A total of 32 age-matched patients with hypertension, but without AF were selected as the control group. The expressions of PPARγ, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA in monocytes were detected by using a reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1 (IL-1) was measured by immunoenzymetric methods. Results: The PPARγ mRNA was markedly decreased in the hypertensive AF group as compared with the hypertensive non-AF group, and it was significantly lower in persistent AF than paroxysmal AF (0.222 ± 0.0702 vs 0.564 ± 0.0436, P<0.01). TNF-α mRNA, IL-6 mRNA, and IL-1 were increased in patients with hypertensive AF compared to the non-AF group and it was even higher in persistent AF than in paroxysmal AF (0.721 ± 0.0541 vs 0.530 ± 0.0496, 0.567 ± 0.044 vs 0.457 ± 0. 0505, 325.61 ± 88.10 vs 190.65 ± 59.38, respectively, P<0.01). TNF-α, IL-6, and IL-1 were in negative correlation with PPARγ, the correlation coefficient was −0.854, −0.769, and −0.702, respectively (P<0.01). Conclusions: In hypertensive patients, increased inflammatory cytokines were associated with increased incidence of AF and atrial remodeling; PPARγ may be involved in the pathogenesis of AF by regulation of inflammation.

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Section: Discussionmentioning

confidence: 88%

“…Human monocytes were isolated and prepared according to the protocol described by Jiang. 18 Experiments were conducted on the same day of blood collection, and all manipulations were carried out under endotoxin-free conditions. 18 …”

Section: Monocyte Preparationmentioning

confidence: 99%

Downregulation of Peroxisome Proliferator‐activated Receptor‐γ Expression in Hypertensive Atrial Fibrillation

Chen¹,

Bing²,

He³

et al. 2009

Clinical Cardiology

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“…Interest in PPARs increased dramatically when they were shown to be activated by medically relevant compounds including nonsteroidal antiinflammatory drugs [Lehmann et al, 1997]. Upregulation of PPARg reduces expression of several mediators of inflammation [Jiang et al, 1998] including MMP-1 in FLS stimulated with IL-1b [Fahmi et al, 2002a]. However, responses of cells to PPAR ligands can be due to activation of PPAR or can be PPAR independent [Fahmi et al, 2002b] actions which appear to be cell and stimulus, and perhaps ligand specific.…”

Section: Discussionmentioning

confidence: 99%

Suppression of fibroblast metalloproteinases by ajulemic acid, a nonpsychoactive cannabinoid acid

Johnson

Stebulis

Rossetti

et al. 2006

J of Cellular Biochemistry

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Production of matrix metalloproteinases (MMP) in joint tissue of patients with inflammatory arthritis facilitates cartilage degradation and bone erosion, and leads to joint deformities and crippling. Thus, MMPs are important targets for agents designed to treat inflammatory arthritis. Oral administration of ajulemic acid (AjA), a synthetic, nonpsychoactive cannabinoid acid, prevents joint tissue injury in rats with adjuvant arthritis. AjA binds to and activates PPARg directly. Therefore, we investigated the influence of AjA on MMP production in human fibroblast-like synovial cells (FLS), and examined the role of PPARg in the mechanism of action of AjA. FLS, treated or not with a PPARg antagonist, were treated with AjA then stimulated with TNFa or IL-1a. Release of MMPs-1, 3, and 9 was measured by ELISA. The influence of AjA on MMP-3 release from stimulated PPARg positive (PPAR þ/À ) and PPARg null (PPAR À/À ) mouse embryonic fibroblasts (MEF) was also examined. Addition of AjA to FLS suppressed production of MMPs whether or not PPARg activation was blocked. Secretion of MMP-3 was also suppressed by AjA in both TNFa-and IL-1a-stimulated PPARg þ/À and PPARg À/À MEF. Suppression of MMP secretion from FLS by AjA appears to be PPARg independent. Prevention by AjA of joint tissue injury and crippling in the rat adjuvant arthritis model may be explained in large part by inhibition of MMPs. These results suggest that AjA may be useful for treatment of patients with rheumatoid arthritis and osteoarthritis.

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“…PPARγ activation reduces monocyte recruitment to atherosclerotic plaques 136. PPARγ also has a modulatory effect on inflammation and is known to decrease monocyte/macrophage production of several inflammatory cytokines 137. There is a large amount of evidence supporting the antiatherosclerotic properties of PPARγ, whether indirectly by improving control of lipid and blood glucose levels or directly by increasing plaque stability and direct actions on ECs, VSMCs, and macrophages 135.…”

Section: Implication Of Noncanonical Wnt Signaling In Vcmentioning

confidence: 99%