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      Downregulation of peroxisome proliferator-activated receptors (PPARs) in nasal polyposis

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      1 , 1 , 1 , 1 ,
      Respiratory Research
      BioMed Central

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          Abstract

          Background

          Peroxisome proliferator-activated receptor (PPAR) α, βδ and γ are nuclear receptors activated by fatty acid metabolites. An anti-inflammatory role for these receptors in airway inflammation has been suggested.

          Methods

          Nasal biopsies were obtained from 10 healthy volunteers and 10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from 22 patients, before and after 4 weeks of local steroid treatment (fluticasone). Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for protein localization and quantification.

          Results

          mRNA expression of PPARα, PPARβδ, PPARγ was found in all specimens. No differences in the expression of PPARs were obtained in nasal biopsies from patients with allergic rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPARα and PPARγ than normal nasal mucosa and these levels were, for PPARγ, further reduced following steroid treatment. PPARγ immunoreactivity was detected in the epithelium, but also found in smooth muscle of blood vessels, glandular acini and inflammatory cells. Quantitative evaluation of the epithelial immunostaining revealed no differences between nasal biopsies from patients with allergic rhinitis and healthy volunteers. In polyps, the PPARγ immunoreactivity was lower than in nasal mucosa and further decreased after steroid treatment.

          Conclusion

          The down-regulation of PPARγ, in nasal polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests that PPARγ might be of importance in long standing inflammations.

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          Most cited references37

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          PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines.

          The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor family of transcription factors, a large and diverse group of proteins that mediate ligand-dependent transcriptional activation and repression. Expression of PPAR-gamma is an early and pivotal event in the differentiation of adipocytes. Several agents that promote differentiation of fibroblast lines into adipocytes have been shown to be PPAR-gamma agonists, including several prostanoids, of which 15-deoxy-delta-prostaglandin J2 is the most potent, as well as members of a new class of oral antidiabetic agents, the thiazolidinediones, and a variety of non-steroidal anti-inflammatory drugs (NSAIDs). Here we show that PPAR-gamma agonists suppress monocyte elaboration of inflammatory cytokines at agonist concentrations similar to those found to be effective for the promotion of adipogenesis. Inhibition of cytokine production may help to explain the incremental therapeutic benefit of NSAIDs observed in the treatment of rheumatoid arthritis at plasma drug concentrations substantially higher than are required to inhibit prostaglandin G/H synthase (cyclooxygenase).
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            Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.

            Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that can be activated by various xenobiotics and natural fatty acids. These transcription factors primarily regulate genes involved in lipid metabolism and also play a role in adipocyte differentiation. We present the expression patterns of the PPAR subtypes in the adult rat, determined by in situ hybridization using specific probes for PPAR-alpha, -beta and -gamma, and by immunohistochemistry using a polyclonal antibody that recognizes the three rat PPAR subtypes. In numerous cell types from either ectodermal, mesodermal, or endodermal origin, PPARs are coexpressed, with relative levels varying between them from one cell type to the other. PPAR-alpha is highly expressed in hepatocytes, cardiomyocytes, enterocytes, and the proximal tubule cells of kidney. PPAR-beta is expressed ubiquitously and often at higher levels than PPAR-alpha and -gamma. PPAR-gamma is expressed predominantly in adipose tissue and the immune system. Our results suggest new potential directions to investigate the functions of the different PPAR subtypes.
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              The PPARalpha-leukotriene B4 pathway to inflammation control.

              Inflammation is a local immune response to 'foreign' molecules, infection and injury. Leukotriene B4, a potent chemotactic agent that initiates, coordinates, sustains and amplifies the inflammatory response, is shown to be an activating ligand for the transcription factor PPARalpha. Because PPARalpha regulates the oxidative degradation of fatty acids and their derivatives, like this lipid mediator, a feedback mechanism is proposed that controls the duration of an inflammatory response and the clearance of leukotriene B4 in the liver. Thus PPARalpha offers a new route to the development of anti- or pro-inflammatory reagents.
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                Author and article information

                Journal
                Respir Res
                Respiratory Research
                BioMed Central (London )
                1465-9921
                1465-993X
                2005
                7 November 2005
                : 6
                : 1
                : 132
                Affiliations
                [1 ]Laboratory of Clinical and Experimental Allergy Research, Department of Otorhinolaryngology, Lund University, Malmö University Hospital, Malmö, Sweden
                Article
                1465-9921-6-132
                10.1186/1465-9921-6-132
                1298337
                16271155
                f159a9ab-d93c-4097-9b70-ad30355d3f34
                Copyright © 2005 Cardell et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 April 2005
                : 7 November 2005
                Categories
                Research

                Respiratory medicine
                Respiratory medicine

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