PPAR and immune system—what do we know?

Zhang, Xia; Young, Howard A.

doi:10.1016/s1567-5769(02)00057-7

Cited by 101 publications

(63 citation statements)

References 123 publications

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“…Furthermore, recent observations suggest that the PPARs, especially PPARa and PPARg, are involved in the regulation of the immune and inflammatory responses. Although both anti-inflammatory and pro-inflammatory effects of PPARs have been reported (Delerive et al, 2001;Moore et al, 2001a;Cabrero et al, 2002;Clark, 2002;Zhang and Young, 2002;Genolet et al, 2004) the role of PPARs in inflammation is not clear.…”

Section: Introductionmentioning

confidence: 99%

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

Leppänen

Sareila

et al. 2007

British J Pharmacology

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Background and purpose: Nitric oxide (NO) production through the inducible nitric oxide synthase (iNOS) pathway is increased in response to pro-inflammatory cytokines and bacterial products. In inflammation, NO has pro-inflammatory and regulatory effects. Peroxisome proliferator-activated receptors (PPARs), members of the nuclear steroid receptor superfamily, regulate not only metabolic but also inflammatory processes. The aim of the present study was to investigate the role of PPARa in the regulation of NO production and iNOS expression in activated macrophages. Experimental approach: The effects of PPARa agonists were investigated on iNOS mRNA and protein expression, on NO production and on the activation of transcription factors NF-kB and STAT1 in J774 murine macrophages exposed to bacterial lipopolysaccharide (LPS). Key results: PPARa agonists GW7647 and WY14643 reduced LPS-induced NO production in a dose-dependent manner as measured by the accumulation of nitrite into the culture medium. However, PPARa agonists did not alter LPS-induced iNOS mRNA expression or activation of NF-kB or STAT1 which are important transcription factors for iNOS. Nevertheless, iNOS protein levels were reduced by PPARa agonists in a time-dependent manner. The reduction was markedly greater after 24 h incubation than after 8 h incubation. Treatment with the proteasome inhibitors, lactacystin or MG132, reversed the decrease in iNOS protein levels caused by PPARa agonists. Conclusions and implications:The results suggest that PPARa agonists reduce LPS-induced iNOS expression and NO production in macrophages by enhancing iNOS protein degradation through the proteasome pathway. The results offer an additional mechanism underlying the anti-inflammatory effects of PPARa agonists.

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Section: Introductionmentioning

confidence: 99%

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

Leppänen

Sareila

et al. 2007

British J Pharmacology

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“…11 Ligand binding activates PPARg, causes heterodimer formation with the retinoic X receptor (RXR) and binding to peroxisome proliferator response elements (PPRE) in the promoter region of responsive genes. This is in contrast to the PPARb/RXR heterodimer that constitutively binds to the DNA.…”

Section: Introductionmentioning

confidence: 99%

Recognition of apoptotic cells by macrophages activates the peroxisome proliferator-activated receptor-γ and attenuates the oxidative burst

et al. 2005

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It is appreciated that phagocytosis of apoptotic cells (AC) is an immunological relevant process that shapes the proversus anti-inflammatory macrophage phenotype. It was our intention to study the respiratory burst, a prototype marker of macrophage activation, under the impact of AC. Following incubation of RAW264.7 macrophages with AC, we noticed attenuated production of reactive oxygen species (ROS) in response to PMA treatment, and observed a correlation between attenuated ROS formation and suppression of protein kinase Ca (PKCa) activation. EMSA analysis demonstrated an immediate activation of peroxisome proliferatoractivated receptor-c (PPARc) following supplementation of AC to macrophages. In macrophages carrying a dominantnegative PPARc mutant, recognition of AC no longer suppressed PKCa activation, and the initial phase of ROS formation was largely restored. Interference with actin polymerization and transwell experiments suggest that recognition of AC by macrophages suffices to attenuate the early phase of ROS formation that is attributed to PPARc activation.

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“…18 One group of synthetic PPAR-c agonistic ligands is the glitazones, drugs used in the treatment of diabetic patients. 19 Several studies have clearly demonstrated that PPAR-c plays an important role in the control of inflammatory responses, 20,21 acting on T cells, 22,23 macrophages, dendritic cells, 24 and mast cells. 25 In monocytes and macrophages PPAR-c agonists inhibit the expression of proinflammatory cytokines, such as TNF-a, IL-1b, and IL-6.…”

mentioning

confidence: 99%

Peroxisome proliferator–activated receptor γ is expressed in airways and inhibits features of airway remodeling in a mouse asthma model☆

Honda

Marquillies

Capron

et al. 2004

Journal of Allergy and Clinical Immunology

134

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PPAR and immune system—what do we know?

Cited by 101 publications

References 123 publications

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

Recognition of apoptotic cells by macrophages activates the peroxisome proliferator-activated receptor-γ and attenuates the oxidative burst

Peroxisome proliferator–activated receptor γ is expressed in airways and inhibits features of airway remodeling in a mouse asthma model☆

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