Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator activated receptor / retinoid X receptor heterodimers in the absence and … (2005 May)
fluorescence imaging reveals the nuclear behavior of peroxisome proliferator activated receptor / retinoid X receptor heterodimers in the absence and presence of ligand . In a global approach combining fluorescence recovery after photobleaching ( FRAP ) , fluorescence correlation spectroscopy ( FCS ) , and fluorescence resonance energy transfer ( FRET ) , we address the behavior in living cells of the peroxisome proliferator activated receptors ( ppars ) , a family of nuclear receptors involved in lipid and glucose metabolism , inflammation control , and wound healing . We first demonstrate that unlike several other nuclear receptors , ppars do not form speckles upon ligand activation . The subnuclear structures that may be observed under some experimental conditions result from overexpression of the protein and our immunolabeling experiments suggest that these structures are subjected to degradation by the proteasome . interestingly and in contrast to a general assumption , ppars readily heterodimerize with retinoid X receptor ( RXR ) in the absence of ligand in living cells . PPAR diffusion coefficients indicate that all the receptors are engaged in complexes of very high molecular masses and / or interact with relatively immobile nuclear components . ppars are not immobilized by ligand binding . however , they exhibit a ligand induced reduction of mobility , probably due to enhanced interactions with cofactors and / or chromatin . Our study draws attention to the limitations and pitfalls of fluorescent chimera imaging and demonstrates the usefulness of the combination of FCS , …

New concepts on the mechanism of action of fibrates and therapeutic prospectives in atherosclerosis peroxisome proliferator activated receptors ( ppars … (2001 Jul)
New concepts on the mechanism of action of fibrates and therapeutic prospectives in atherosclerosis peroxisome proliferator activated receptors ( ppars ) have been discovered 10 years ago as being orphan nuclear receptors . three subtypes of PPAR ( s ) have been identified ( alpha , gamma , delta ) . activated ppars bind to peroxisome proliferator response element which are localized in numerous gene promoters . PPAR ( s ) are activated by fatty acids and eicosanoids . PPAR alpha activators ( fibrates ) improve plasma lipid levels and decrease CHD risk in patients with low HDL cholesterol ( gemfibrozil ) . They also decrease atherogenesis ( fenofibrate ) in patients with type 2 diabetes . these drugs decrease atherogenic lipoprotein plasma levels such as VLDL and small dense LDL and they increase anti atherogenic HDL , through increases in apo A I and apo A II synthesis . furthermore , they induce overexpression in HDL receptors , such as SR BI / CLA 1 and abca1 which are capable to increase cellular cholesterol efflux . therefore , fibrates would reduce atherogenesis through their capacity to increase the reverse cholesterol transport . moreover , they would reduce vascular inflammation by repressing NF kappa B and AP I transcriptional activity and they would reduce thrombosis risk by inhibiting tissue factor and fibrinogen synthesis .

Vascular inflammation is negatively autoregulated by interaction between ccaat / enhancer binding protein delta and peroxisome proliferator activated receptor gamma. (2002 Sep)
vascular inflammation is negatively autoregulated by interaction between ccaat / enhancer binding protein delta and peroxisome proliferator activated receptor gamma . ccaat / enhancer binding proteins ( C / EBPs ) upregulate transcription of various inflammatory cytokines and acute phase proteins , such as interleukin ( IL ) 1beta , IL 6 , tumor necrosis factor alpha , and cyclooxygenase 2 . recent studies have demonstrated that peroxisome proliferator activated receptor ( PPAR ) gamma is present in atherosclerotic lesions , and negatively regulates expression of these genes . interestingly , PPAR gamma gene promoter has tandem repeats of C / EBP binding motif , and C / EBP delta plays a pivotal role in transactivation of PPAR gamma gene . It has been well known that the interaction between C / EBPs and PPAR gamma plays a central role in maintaining adipocyte differentiation and glucometabolism ; however , the relationship between PPAR gamma and C / EBPs in the vessel wall remains unclear . In the present study , we showed that a high level of C / EBP delta expression induced by inflammation positively regulated transcription and protein expression of PPAR gamma in vascular smooth muscle cells ( vsmcs ) . On the other hand , PPAR gamma ligands troglitazone , pioglitazone , and 15 deoxy delta ( 12 , 14 ) prostaglandin J ( 2 ) inhibited IL 1beta induced IL 6 expression at a transcriptional revel in vsmcs . functional promoter analysis revealed that PPAR gamma …

The role of the orphan nuclear receptor Rev Erb alpha in adipocyte differentiation and function. (2005 Feb)
The role of the orphan nuclear receptor Rev Erb alpha in adipocyte differentiation and function . lipid and carbohydrate homeostasis in higher organisms is governed by an integrated system that has a capacity to rapidly respond to metabolic changes . numerous signals reciprocally convey information about body fat status from the periphery to central nervous system in the attempt to maintain body weight nearly stable throughout life . The role of adipocyte in energy homeostasis extends its function as a simple energy storage cell . indeed , adipose tissue not only secretes fatty acids , but is also an active endocrine and paracrine organ due to the production of secreted proteins and lipid indicators collectively called adipokines . these observations have spurred interest in the identification of the transcriptional and other regulatory pathways of adipocyte differentiation . The nuclear receptor , peroxisome proliferator activated receptor gamma ( PPAR gamma ) ( nr1c3 ) and members of the ccaat enhancer binding protein ( C / EBP ) family are central mediators controlling adipocyte differentiation and function . Rev erb alpha ( nr1d1 ) is an orphan nuclear receptor encoded on the opposite strand of the thyroid receptor alpha gene . Rev erb alpha acts as a negative regulator of transcription binding to the same response element than another orphan nuclear receptor , ROR alpha . Rev erb alpha is highly expressed in adipose tissue , skeletal muscle , heart , liver and brain . Rev erb alpha expression increases during adipocyte …

Contribution of inflammatory processes to alzheimer s disease : molecular mechanisms. (2006 Feb)
contribution of inflammatory processes to alzheimer s disease : molecular mechanisms . there is compelling evidence that alzheimer s disease ( AD ) amyloid beta ( abeta ) deposition is associated with a local inflammatory response , which is initiated by the activation of microglia and the recruitment of astrocytes . these cells secrete a number of cytokines and neurotoxic products that may contribute to neuronal degeneration and cell death . It has been documented that long term intake of non steroidal anti inflammatory drugs ( nsaids ) decrease the risk for developing AD and delay the onset of the disease . The mechanism behind these nsaids is still controversial and several hypotheses have been raised , including changes in the amyloid precursor protein ( APP ) metabolism , in abeta aggregation and a decrease in inflammatory mediators . recently , it was proposed that some nsaids might activate the peroxisome proliferator activated receptor gamma ( PPAR gamma ) . PPAR gamma belongs to a family of nuclear receptors that are able to regulate the transcription of pro inflammatory molecules , such as iNOS . The activation of PPAR gamma has been recently reported to reduce abeta levels in cell culture and AD animal models . The implication of PPAR gamma in the control of abeta induced inflammation suggests a new target for AD therapy and emphasize the contribution of neuroinflammatory mechanisms to the pathogenesis of AD .

Pparalpha ligands reduce PCB induced endothelial activation : possible interactions in inflammation and atherosclerosis. (2007 Nov)
pparalpha ligands reduce PCB induced endothelial activation : possible interactions in inflammation and atherosclerosis . exposure to polychlorinated biphenyls ( PCBs ) can activate inflammatory responses in vascular endothelial cells . activation of peroxisome proliferator activated receptors ( ppars ) by nutrients or synthetic agonists has been shown to block pro inflammatory responses both in vitro and in vivo . Here we demonstrate that activation of pparalpha by synthetic agonists can reduce 3 , 3 4 , 4 tetrachlorobiphenyl ( pcb77 ) induced endothelial cell activation . primary vascular endothelial cells were pretreated with the pparalpha ligands fenofibrate or wy14643 followed by exposure to pcb77 . pparalpha activation protected endothelial cells against pcb77 induced expression of the pro inflammatory proteins vascular cell adhesion molecule 1 ( VCAM 1 ) , cycloxygenase 2 ( COX 2 ) , and pcb77 induced expression and activity of the aryl hydrocarbon receptor ( AHR ) responsive cytochrome P450 1A1 ( cyp1a1 ) . furthermore , basal AHR expression was downregulated by fenofibrate and wy14643 . We also investigated the possible interactions between PCBs , and basal PPAR activity and protein expression . treatment with pcb77 significantly reduced basal mRNA expression of pparalpha and the PPAR responsive gene cyp4a1 , as well as pparalpha protein expression . Also , pcb77 exposure caused a significant decrease in basal PPAR dependent reporter gene expression in MCF 7 cells . overall , these findings suggest that pparalpha agonists can reduce pcb77 induction of endothelial cell activation by inhibition …

Peroxisome proliferator activated receptors as new molecular targets in psoriasis. (2004 Jun)
peroxisome proliferator activated receptors as new molecular targets in psoriasis . while psoriasis is upon the age of biological treatments , additional researches have led to other new therapies for psoriasis , including targets aimed at nuclear receptors . ppars are members of the nuclear hormone receptor superfamily , including retinoid receptors and vitamin D receptors . recent works have highlighted the role of ppars , which transduce a wide variety of signals into a set of cellular responses at the level of gene transcription , as critical regulators of cutaneous homeostasis in regulating differentiation , proliferation , and inflammatory responses of the skin . PPAR agonists or antagonists may therefore , hold promise as interesting compounds for the treatment of various epidermal disorders characterized by inflammation , hyperproliferation and aberrant differentiation , such as psoriasis .

Transcription coactivators for peroxisome proliferator activated receptors. (2007 Aug)
transcription coactivators for peroxisome proliferator activated receptors . peroxisome proliferator activated receptors ( ppars ) regulate diverse biological processes such as development , differentiation , neoplastic conversion , inflammation and wound healing in addition to their critical roles in energy ( lipid and carbohydrate ) metabolism . unliganded ppars heterodimerize with retinoid X receptor alpha and repress transcription when bound to DNA by interacting with corepressor molecules . Upon canonical ligand binding , ppars manifest conformational changes that facilitate the dissociation of corepressor molecules to enable a spatiotemporally orchestrated recruitment ( association ) of coactivators and coactivator associated proteins to the liganded receptor . functional significance for the existence of over 200 nuclear receptor cofactors is not readily evident , but emerging gene knockout mouse models show that some of the coactivators are essential for embryonic growth and survival and for controlling receptor specific target gene expression in a cell specific need based demands . coactivators contain one or more highly conserved lxxll amphiphatic alpha helix motif , called nuclear receptor box , for direct interaction with the activation function 2 ( AF 2 ) regions in nuclear receptors . ppars interact with large multisubunit coactivator protein complexes , some exhibiting intrinsic histone acetyltransferase or methyltransferase activity , while others functioning as facilitators of ATP dependent chromatin remodeling or as linkers to the basal transcription machinery . while the dynamic and coordinated changes in nuclear receptor expression and differences in the nature of their key target genes are important , …

The central role of fat and effect of peroxisome proliferator activated receptor gamma on progression of insulin resistance and cardiovascular … (2003 Sep)
The central role of fat and effect of peroxisome proliferator activated receptor gamma on progression of insulin resistance and cardiovascular disease . recent evidence suggests that progression of insulin resistance parallels progression of atherosclerosis . Fat plays an integral role in the development of type 2 diabetes and vascular injury . The balance of adipose derived substances , including free fatty acids , tumor necrosis factor alpha , leptin , adiponectin , and plasminogen activator inhibitor 1 , determine both insulin action and the state of vascular inflammation . peroxisome proliferator activated receptor gamma ( PPAR gamma ) ligands promote the balance of these substances to enhance insulin mediated glucose uptake and decrease inflammation . PPAR gamma ligands reverse the major defect of the insulin resistance syndrome and have important effects that inhibit atherosclerosis , improve endothelial cell function , and attenuate inflammation . although more research is needed , data suggest that PPAR gamma ligands may prevent the progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis .

Topical peroxisome proliferator activated receptor alpha activators reduce inflammation in irritant and allergic contact dermatitis models. (2002 Feb)
topical peroxisome proliferator activated receptor alpha activators reduce inflammation in irritant and allergic contact dermatitis models . activators of peroxisome proliferator activated receptor alpha , a nuclear hormone receptor that heterodimerizes with retinoid X receptor , stimulate epidermal differentiation and inhibit proliferation . Here we determined the anti inflammatory effects of peroxisome proliferator activated receptor alpha agonists in models of irritant and allergic contact dermatitis produced in mouse ears by topical treatment with 12 O tetradecanoylphorbol 13 acetate and oxazalone , respectively . As expected , 12 O tetradecanoylphorbol 13 acetate treatment resulted in a marked increase in the thickness and weight of the ears and provoked an inflammatory cell infiltrate in the dermis . topical treatment with three different peroxisome proliferator activated receptor alpha agonists , clofibrate , WY 14643 , or linoleic acid , 45 min and 4 h after 12 O tetradecanoylphorbol 13 acetate application , resulted in a marked decrease in ear thickness and weight and a reduction in the number of inflammatory cells in the dermis . The reduction in inflammation by these peroxisome proliferator activated receptor alpha agonists was of similar magnitude to that seen with a potent topical glucocorticoid , clobetasol . In contrast , stearic acid , a free fatty acid that does not activate peroxisome proliferator activated receptor alpha , had no effect on the 12 O tetradecanoylphorbol 13 acetate induced inflammation . moreover , clofibrate did not significantly alter ear thickness following 12 O tetradecanoylphorbol 13 acetate treatment in peroxisome …

Diverse regulation of NF kappab and peroxisome proliferator activated receptors in murine nonalcoholic fatty liver. (2004 Sep)
diverse regulation of NF kappab and peroxisome proliferator activated receptors in murine nonalcoholic fatty liver . fatty liver is highly sensitive to inflammatory activation . peroxisome proliferator activated receptors ( PPAR ) have anti inflammatory effects and regulate lipid metabolism in the fatty liver . We hypothesized that fatty liver leads to endotoxin sensitivity through an imbalance between pro and anti inflammatory signals . leptin deficient , ob / ob mice and their lean littermates were challenged with single or double insults and pro and anti inflammatory pathways were tested on cytokine production and activation of nuclear regulatory factors NF kappab and peroxisome proliferator receptor element ( PPRE ) . Ob / ob mice produced significantly higher serum tumor necrosis factor alpha ( TNF alpha ) and interleukin ( IL ) 6 and showed increased hepatic NF kappab activation compared to lean littermates after stimulation with a single dose of lipopolysaccharide ( LPS ) or alcohol . In ob / ob mice , double insults with alcohol and LPS augmented proinflammatory responses mediated by increased degradation of inhibitory kappab ( ikappab ) alpha and ikappab beta and preferential induction of the p65 / p50 NF kappab heterodimer . In lean mice , in contrast , acute alcohol attenuated LPS induced TNF alpha , IL 6 production , and NF kappab activation through reduced ikappab alpha degradation and induction of p50 / p50 homodimers . PPRE binding was increased in fatty but not in lean livers after alcohol or LPS stimulation …

Peroxisome proliferator activated receptor alpha target genes. (2004 Mar)
peroxisome proliferator activated receptor alpha target genes . peroxisome proliferator activated receptors ( ppars ) are nuclear proteins that belong to the superfamily of nuclear hormone receptors . They mediate the effects of small lipophilic compounds such as long chain fatty acids and their derivatives on transcription of genes commonly called PPAR target genes . Here we review the involvement of pparalpha in peroxisomal and mitochondrial fatty acid oxidation , microsomal fatty acid hydroxylation , lipoprotein , bile and amino acid metabolism , glucose homeostasis , biotransformation , inflammation control , hepato carcinogenesis and other pathways , through a detailed analysis of the different known or putative pparalpha target genes .

The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis. (2001 Apr)
The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis . peroxisome proliferator activated receptor ( PPAR ) gamma is a nuclear hormone receptor that serves as a trans factor to regulate lipid metabolism . intense interest is focused on PPAR gamma and its ligands owing to its putative role in adipocyte differentiation . little is known , however , about the functions of PPAR gamma in the immune system , especially in T lymphocytes . We demonstrate that both naive and activated ovalbumin specific T cells from DO11 . 10 transgenic mice express PPAR gamma mRNA and protein . In order to determine the function of PPAR gamma , T cells were stimulated with phorbol 12 myristate 13 acetate and ionomycin or antigen and antigen presenting cells . simultaneous exposure to PPAR gamma ligands ( e . g . 15 deoxy delta ( 12 , 14 ) prostaglandin J ( 2 ) , troglitazone ) showed drastic inhibition of proliferation and significant decreases in cell viability . The decrease in cell viability was due to apoptosis of the T lymphocytes , and occurred only when cells were treated with PPAR gamma , and not PPAR alpha agonists , revealing specificity of this response for PPAR gamma . these observations suggest that PPAR gamma agonists play an important role in regulating T cell mediated immune responses by inducing apoptosis . T cell death via PPAR gamma ligation may act as a potent anti …

Rosiglitazone , an agonist of peroxisome proliferator activated receptor gamma , protects against gastric ischemia reperfusion damage in rats : … (2004 Nov)
rosiglitazone , an agonist of peroxisome proliferator activated receptor gamma , protects against gastric ischemia reperfusion damage in rats : role of oxygen free radicals generation . peroxisome proliferator activated receptor gamma ( PPAR gamma ) is a nuclear hormone receptor super family that has recently been implicated in atherosclerosis , inflammation , cancer , infertility , and demyelination . oxidative stress , neutrophil infiltration , proinflammatory cytokines , and the exhibition of luminal acid play a role in the pathogenesis of gastric injury induced by ischemia reperfusion . rosiglitazone , a specific PPAR gamma ligand , has been shown to have antiinflammatory activity , but its effects on experimental ischemia reperfusion gastric injury remain unknown . We have investigated the effects of the rosiglitazone on gastric injury caused by ischemia following reperfusion in rats . tumour necrosis factor alpha ( TNF alpha ) levels and changes in enzymatic activities of myeloperoxidase , as a marker of neutrophils infiltration , xanthine oxidase , superoxide dismutase , and glutathione peroxidase , were determined . histological analysis of the lesions was also carried out . pretreatment with 1 or 4 mg / kg of rosiglitazone ameliorated the gastric damage induced by clamping the celiac artery for 30 min followed by 60 min of reperfusion . It significantly ( P 0 . 05 ) reduced the index of neutrophil infiltration and the levels of the cytokine . rosiglitazone did not revert the reduced glutathione peroxidase activity but enhanced significantly ( P 0 . …

Ligands of peroxisome proliferator activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. (2000 Aug)
ligands of peroxisome proliferator activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells . background AIMS : proliferation and migration of hepatic stellate cells ( HSCs ) and expression of chemokines are involved in the pathogenesis of liver inflammation and fibrogenesis . peroxisome proliferator activated receptor ( PPAR ) gamma is a receptor transcription factor that controls growth and differentiation in different tissues . We explored the effects of PPAR gamma agonists on the biological actions of cultured human HSCs . methods : HSCs were isolated from normal human liver tissue and used in their myofibroblast like phenotype or immediately after isolation . activation of PPAR gamma was induced with 15 deoxy delta ( 12 , 14 ) prostaglandin J ( 2 ) or with troglitazone . results : PPAR gamma agonists dose dependently inhibited HSC proliferation and chemotaxis induced by platelet derived growth factor . This effect was independent of changes in postreceptor signaling or expression of c fos and c myc and was associated with inhibition of cell cycle progression beyond the G ( 1 ) phase . activation of PPAR gamma also resulted in a complete inhibition of the expression of monocyte chemotactic protein 1 at the gene and protein levels . comparison of quiescent and culture activated HSCs revealed a marked decrease in PPAR gamma expression in activated cells . conclusions : activation of PPAR gamma modulates profibrogenic and proinflammatory actions in HSCs . reduced PPAR gamma expression may contribute to confer an …

Peroxisome proliferator activated receptor beta as a target for wound healing drugs. (2004 Mar)
peroxisome proliferator activated receptor beta as a target for wound healing drugs . healing of cutaneous wounds , which is crucial for survival after an injury , proceeds via a well tuned pattern of events including inflammation , re epithelialisation , and matrix and tissue remodelling . these events are regulated spatio temporally by a variety of growth factors and cytokines . The inflammation that immediately follows injury increases the expression of peroxisome proliferator activated receptor ( PPAR ) beta in the wound edge keratinocytes and triggers the production of endogenous pparbeta ligands that activate the newly produced receptor . This elevated pparbeta activity results in increased resistance of the keratinocytes to the apoptotic signals released during wounding , allowing faster re epithelialisation . The authors speculate that , in parallel , ligand activation of pparbeta in infiltrated macrophages attenuates the inflammatory response , which also promotes repair . Thus , current understanding of the roles of pparbeta in different cell types implicated in tissue repair has revealed an intriguing intercellular cross talk that coordinates , spatially and temporally , inflammation , keratinocyte survival , proliferation and migration , which are all essential for efficient wound repair . these novel insights into the orchestrating roles of pparbeta during wound healing may be helpful in the development of drugs for acute and chronic wound disorders .

Peroxisome proliferator activated receptors and liver X receptors in atherosclerosis and immunity. (2006 Feb)
peroxisome proliferator activated receptors and liver X receptors in atherosclerosis and immunity . atherosclerosis is a primary cause of death in the united states , and the current obesity epidemic threatens to exacerbate its morbidity and mortality worldwide . despite important cardiovascular treatment advances over the past few decades , new approaches are needed to curb dangerous health trends . nuclear receptors are a superfamily of ligand activated transcription factors . The discovery of subfamilies known as peroxisome proliferator activated receptors ( PPAR ) and liver X receptors ( LXR ) as lipid sensors that regulate lipid and glucose metabolism as well as inflammation offers new targets for nutritional and pharmacologic treatment of cardiovascular disease .

Antiinflammatory roles of peroxisome proliferator activated receptor gamma in human alveolar macrophages. (2004 Jan)
antiinflammatory roles of peroxisome proliferator activated receptor gamma in human alveolar macrophages . peroxisome proliferator activated receptor gamma ( ppargamma ) is a ligand activated transcriptional factor belonging to the nuclear receptor superfamily . ppargamma , which is predominantly expressed in adipose tissue , plays a major regulatory role in glucose metabolism and adipogenesis . interestingly , recent studies have demonstrated ppargamma expression in monocytes / macrophages and its antiinflammatory activities . however , it is unclear whether alveolar macrophages ( AMs ) express functional ppargamma . The present study was conducted to investigate the expression of ppargamma by AMs and to elucidate its functional role . using reverse transcription polymerase chain reaction and western blotting , we demonstrated the strong expression of ppars messenger RNA and protein in freshly isolated human AMs . ligands of ppargamma , 15 deoxy delta ( 12 , 14 ) prostaglandin J2 , and troglitazone significantly decreased LPS induced tumor necrosis factor alpha production by AMs . these ligands markedly upregulated the expression of CD36 , a scavenger receptor that mediates the phagocytosis of apoptotic neutrophils . indeed , ligand treated AMs ingested a significantly higher number of apoptotic neutrophils than untreated AMs . these data indicate that ppargamma expressed by AMs play an antiinflammatory role through inhibiting cytokine production and increasing their CD36 expression together with the enhanced phagocytosis of apoptotic neutrophils , which is an essential process for the resolution of inflammation . This suggests the potential therapeutic application of ppargamma ligands …

Peroxisome proliferator activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis. (2003 Dec)
peroxisome proliferator activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis . The ligand activated transcription factor , peroxisome proliferator activated receptor gamma ( PPAR gamma ) , has pleiotropic effects on lipid and glucose metabolism as well as modulating immune activity . In Th1 predominant models of inflammatory bowel disease and arthritis , PPAR gamma ligands can ameliorate clinical disease severity , partly by downregulating a range of inflammatory cytokines . however , PPAR gamma has not been evaluated in chronic sarcoidosis , a disease characterized by persistent activation of Th1 immune responses in alveolar macrophages . We hypothesized that a deficiency of PPAR gamma activity contributes to ongoing inflammation in pulmonary sarcoidosis via failure to repress proinflammatory transcription factors . To address this , we studied eight patients with active sarcoidosis and nine healthy control subjects by bronchoscopy . bronchoalveolar lavage specimens from patients revealed a striking reduction of PPAR gamma activity by electrophoretic mobility shift assay in alveolar macrophages compared with healthy control subjects , with a concomitant upregulation of nuclear factor ( NF ) kappa B activity . immunostaining and real time polymerase chain reaction demonstrated reductions of PPAR gamma nuclear protein and gene expression . The data show for the first time that alveolar macrophages from patients with active sarcoidosis exhibit activation of NF kappa B and deficiency of PPAR gamma . although these results do not demonstrate a direct causal effect , they are consistent with the hypothesis that insufficient PPAR …

Peroxisome proliferator activated receptor gamma activators inhibit interleukin 12 production in murine dendritic cells. (2001 Jan)
peroxisome proliferator activated receptor gamma activators inhibit interleukin 12 production in murine dendritic cells . peroxisome proliferator activated receptors ( ppars ) are members of the nuclear receptor superfamily . They are divided into three subtypes ( alpha , beta or delta , and gamma ) and are involved in lipid and glucose homeostasis and in the control of inflammation . In this study , we analyzed the expression of ppars in murine dendritic cells ( DCs ) , the most potent antigen presenting cells . We find that immature as well as mature spleen derived DCs express ppargamma , but not pparalpha , mRNA and protein . We also show that the ppargamma activator rosiglitazone does not interfere with the maturation of DCs in vitro nor modifies their ability to activate naive T lymphocytes in vivo . finally , we present evidence that ppargamma activators down modulate the CD40 induced secretion of interleukin 12 , a potent Th1 driving factor . these data suggest a possible role for ppargamma in the regulation of immune responses .