Removal of Chromium (III) and Reduction in Toxicity in a Primary Tannery Effluent Using Two Floating Macrophytes.

Trivalent chromium (Cr(III)) is a contaminant with toxic activity. Its presence in waters and soils is usually related to industrial activities such as tanneries. The aim of this study was to compare the removal of Cr(III) in hydroponic solutions and tannery effluents using two floating macrophytes: Salvinia auriculata and Eichhornia crassipes. First, to determine the chromium removal capacity in solution and the bioaccumulation factor (BAF) in tissues of each plant, experiments were set up with contaminated solutions with Cr(III) concentrations of 2, 5, 10, 20, and 40 mg/L. Subsequently, both plant species were exposed to a primary tannery effluent contaminated with 12 mg/L of Cr(III) in order to study the removal capacity of organic and inorganic matter, as well as the acute toxicity in the water flea (Daphnia magna) and genotoxicity in zebrafish (Danio rerio). Tests carried out on nutrient solutions revealed that both plants have a high capacity for removing Cr(III) in solution. The BAF in tissues was higher in E. crassipes compared to S. auriculata. In the experiments with a tannery effluent, both species presented low nutrient and organic matter removal efficiency, but they showed good Cr(III) removal capacity, with average reduction values of 57% for S. auriculata and 54% for E. crassipes after 72 h of exposure. E. crassipes contributed most to the reduction in acute toxicity in D. magna, while S. auriculata did not show a similar effect. However, both plant species managed to reduce the genotoxicity marker in D. rerio when compared with the initial effluent and the control.

Physical Evidence of Oil Uptake and Toxicity Assessment of Amphiphilic Grafted Nanoparticles Used as Oil Dispersants.

Herein, we report the toxicity evaluation of a new prototype dispersant system, silicon dioxide nanoparticles (NPs) functionalized with (3-glycidoxypropyl)triethoxysilane (GPS) and grafted poly(ε-caprolactone)-block-poly[oligo(ethylene glycol)methyl methacrylate mono-methyl ether] (NP-PCL-POEGMA). This serves as a follow up of our previous study where grafted silicon dioxide NPs functionalized with GPS and grafted hyperbranched poly(glycidol) (NP-HPG) were evaluated for reducing the toxicity in embryo, juvenile, and adult fish populations. In this study, the NP-HPG sample is used as a baseline to compare against the new NP-PCL-POEGMA samples. The relative size was established for three NP-PCL-POEGMA samples via cryogenic transmission electron microscopy. A quantitative mortality study determined that these NPs are non-toxic to embryo populations. An ethoxyresorufin-O-deethylase assay was performed on these NP-PCL-POEGMA samples to test for reduced cytochrome P450 1A after the embryos were exposed to the water-accommodated fraction of crude oil. Overall, these NP-PCL-POEGMA NPs better protected the embryo populations than the previous NP-HPG sample (using a protein activity end point), showing a trend in the right direction for prototype dispersants to replace the commercially utilized Corexit.

Towards regulation of Endocrine Disrupting chemicals (EDCs) in water resources using bioassays - A guide to developing a testing strategy.

Endocrine disrupting chemicals (EDCs) are found in every environmental medium and are chemically diverse. Their presence in water resources can negatively impact the health of both human and wildlife. Currently, there are no mandatory screening mandates or regulations for EDC levels in complex water samples globally. Bioassays, which allow quantifying in vivo or in vitro biological effects of chemicals are used commonly to assess acute toxicity in water. The existing OECD framework to identify single-compound EDCs offers a set of bioassays that are validated for the Estrogen-, Androgen-, and Thyroid hormones, and for Steroidogenesis pathways (EATS). In this review, we discussed bioassays that could be potentially used to screen EDCs in water resources, including in vivo and in vitro bioassays using invertebrates, fish, amphibians, and/or mammalians species. Strengths and weaknesses of samples preparation for complex water samples are discussed. We also review how to calculate the Effect-Based Trigger values, which could serve as thresholds to determine if a given water sample poses a risk based on existing quality standards. This work aims to assist governments and regulatory agencies in developing a testing strategy towards regulation of EDCs in water resources worldwide. The main recommendations include 1) opting for internationally validated cell reporter in vitro bioassays to reduce animal use & cost; 2) testing for cell viability (a critical parameter) when using in vitro bioassays; and 3) evaluating the recovery of the water sample preparation method selected. This review also highlights future research avenues for the EDC screening revolution (e.g., 3D tissue culture, transgenic animals, OMICs, and Adverse Outcome Pathways (AOPs)).

Toxicity assessment of a novel oil dispersant based on silica nanoparticles using Fathead minnow.

Oil spill accidents are a major concern for aquatic organisms. In recent history, the Deepwater Horizon blowout spilled 500 million liters of crude oil into the Gulf of Mexico. Corexit 9500A was used to disperse the oil since it was the method approved at that time, despite safety concerns about its use. A better solution is necessary for dispersing oil from spills that reduces the toxicity to exposed aquatic organisms. To address this challenge, novel engineered nanoparticles were designed using silica cores grafted with hyperbranched poly(glycidol) branches. Because the silica core and polymers are known to be biocompatible, we hypothesized that these particles are nontoxic to fathead minnows (Pimephales promelas) and would decrease their exposure to oil polyaromatic hydrocarbons. Fathead minnow embryos, juveniles and adult stages were exposed to the particles alone or in combination with a water-accommodated fraction of oil. Acute toxicity of nanoparticles to fish was tested by measuring mortality. Sub-lethal effects were also measured including gene expression of cytochrome P450 1a (cyp1a) mRNA and heart rate in embryos. In addition, a mixture of particles plus the water-accommodated fraction was directly introduced to adult female fathead minnows by gavage. Three different nanoparticle concentrations were used (2, 10, and 50 mg/L) in either artificial fresh water or the water-accommodated fraction of the oil. In addition, nanoparticle-free controls were carried out in the two solutions. No significant mortality was observed for any age group or nanoparticle concentration, suggesting the safety of the nanoparticles. In the presence of the water-accommodated fraction alone, juvenile and adult fathead minnows responded by increasing expression of cyp1a. The addition of nanoparticles to the water-accommodated fraction reduced cyp1a gene expression in treatments. Heart rate was also restored to normal parameters in embryos co-exposed to nanoparticles and to the water-accommodated fraction. Measurement of polyaromatic hydrocarbons confirmed their presence in the tested solutions and the reduction of available PAH in WAF treated with the nanoparticles. Our findings suggest the engineered nanoparticles may be protecting the fish by sequestering polyaromatic hydrocarbons from oil, measured indirectly by the induction of cypa1 mRNAs. Furthermore, chemical analysis showed a reduction in PAH content in the water accommodated fraction with the presence of nanoparticles.

Correction: Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis.

[This corrects the article DOI: 10.1371/journal.pone.0120386.].

Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.

Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation.

Adiponectin attenuates human eosinophil adhesion and chemotaxis: implications in allergic inflammation.

OBJECTIVE: Growing evidence has shown an association between obesity and asthma. Adiponectin, an adipocyte-derived cytokine, is known to have anti-inflammatory effects with reduced concentrations in obese subjects. Recent findings raised the intriguing possibility that adiponectin might play a role in allergic inflammation, although the mechanistic basis for their relationship remains unclear. The purpose of this study was to examine whether adiponectin might affect functions of eosinophils, which play an important role in the pathogenesis of asthma. METHODS: Human peripheral blood eosinophils were purified to study expression of adiponectin receptors AdipoR1 and AdipoR2 using RT-PCR and flow cytometry. The effect of adiponectin on eosinophil survival was investigated using annexin V and propidium iodide staining. Eotaxin-induced cell adhesion was investigated using ICAM-1-coated plates. A Boyden chamber and real-time horizontal migration system were used for eotaxin-directed chemotaxis assay. Expression of eotaxin receptor CCR3 and intracellular calcium influx were assessed by flow cytometry. RESULTS: AdipoR1 and AdipoR2 were expressed in human eosinophils. Adiponectin did not affect eosinophil survival or CCR3 expression; however, eotaxin-enhanced adhesion was inhibited by pretreatment with adiponectin. Adiponectin also diminished eotaxin-directed chemotactic responses by disturbing both velocity and directionality. Calcium influx in response to eotaxin was attenuated by adiponectin. CONCLUSIONS: These results indicate that adiponectin attenuates the eosinophil functions induced by eotaxin without affecting cell viability. The inhibitory effect was associated with diminished calcium signaling rather than altering of surface receptor expression. Increasing circulating adiponectin might be a novel therapeutic modality for treatment of asthma, especially in obese asthmatics.

Retinoic acids are potent inhibitors of spontaneous human eosinophil apoptosis.

Retinoic acids (RAs), which are active metabolites of vitamin A, are known to enhance Th2-type immune responses in vitro, but the role of RAs in allergic inflammatory cells remains unclear. In this study, we demonstrated that purified peripheral blood eosinophils expressed nuclear receptors for RAs at the mRNA and protein levels. Eosinophils cultured with all-trans RA (ATRA) and 9-cis-RA showed dramatically induced cell survival and nuclear hypersegmentation, and the efficacy of RAs (10(-6)M) was similar to that of IL-5 (1 ng/ml), the most critical cytokine for eosinophil activation. Pharmacological manipulation with receptor-specific agonists and antagonists indicated that the antiapoptotic effect of RAs was mediated through ligand-dependent activation of both retinoid acid receptors and retinoid X receptors (mainly retinoid acid receptors). Furthermore, using a gene microarray and a cytokine Ab array, we discovered that RAs induced vascular endothelial growth factor, M-CSF, and MCP-1 secretion, although they were not involved in eosinophil survival. RA-induced eosinophil survival appears to be associated with down-regulation of caspase 3 and inhibition of its enzymatic activity. These findings indicate an important role of RAs in homeostasis of granulocytes and provide further insight into the cellular and molecular pathogenesis of allergic reactions.

EG2 expressed by eosinophils as a clinically useful indicator of asthma.

The monitoring of airway inflammation is mandatory for the improved control of bronchial asthma. We previously reported that intracellular EG2 levels of eosinophils, a marker of bronchial asthma increased in asthma patients. In this study, we hypothesized that eosinophil EG2(+) expression increases during airway inflammation in asthmatic individuals. Eosinophil EG2(+) and percentage eosinophil EG2(+) with whole blood flow cytometry, eosinophil counts, serum total IgE, serum eosinophil cationic protein, eosinophil-derived neurotoxin, and percent of forced expiratory volume in 1 second/force vital capacity (FEV(1)/FVC) were measured in 33 asthmatic patients and 22 healthy volunteers. The relationships between these markers were evaluated. Comparisons were made on EG2(+) expression between attack and asymptomatic periods in six asthmatic patients. EG2(+) expression was significantly greater in the asthmatic patients than in healthy subjects. Furthermore, the EG2(+) expression showed a significant increase during attacks. EG2(+) expression inversely correlated with the FEV(1)/FVC. These results suggest that EG2(+) expression may be a useful clinical marker of airway inflammation in asthma.

Possible novel receptor for PGD2 on human bronchial epithelial cells.

Prostaglandin D(2) (PGD(2)), a major prostanoid produced by activated mast cells, has long been implicated in allergic diseases. Recent studies have shown that PGD(2) exerts its effects through two different G-protein-coupled receptors (GPCRs), the D-prostanoid receptor (DP) and the chemoattractant receptor-homologous molecule expressed on T helper type-2 cells (CRTH2), expressed in various human tissues. The PGD(2)/CRTH2 system mediates the chemotaxis of eosinophils, basophils, and Th2 cells, which are involved in the induction of allergic inflammation. We have reported that normal human bronchial epithelial cells (NHBE) and epithelial cell lines (NCI-H(292)) expressed CRTH2, and PGD(2) induces production of IL-8 and GM-CSF. This review discusses the role of CRTH2/DP on epithelial cells and mentions a possible novel receptor for PGD(2).

RANTES production from mononuclear cells in response to the specific allergen in asthma patients.

BACKGROUND: Eosinophils are considered to be the major inflammatory cells in asthma. Since regulated on activation, normal T expressed and secreted (RANTES) is a potent chemoattractant for various important inflammatory cells such as eosinophils as well as memory T cells potentially recruiting these cells to an inflamed focus, RANTES has been considered to play a key role in various allergic disorders such as asthma. METHODS: To extend our understanding of the participation of eosinophils and T cells in relation to the production of RANTES in response to the specific allergen in asthma, we examined the production of RANTES from peripheral blood mononuclear cells cultured with specific allergen in atopic asthma patients by a sandwich enzyme-linked immunosorbent assay. RESULTS: It was revealed that mononuclear cells produced RANTES but not eotaxin in response to the specific allergen in asthma. RANTES production from mononuclear cells of asthma patients with eosinophilia was greater than that of asthma patients without eosinophilia. Moreover, in this study, no differences in RANTES production between CD4 negative cells and CD8 negative cells were observed. CONCLUSIONS: Taken together, these findings may suggest that mononuclear cells play a crucial role in the pathogenesis, particular in eosinophil and T lymphocyte recruitment into the inflamed focus of asthma through RANTES production in response to the specific allergen.

Prostaglandin D2 induces IL-8 and GM-CSF by bronchial epithelial cells in a CRTH2-independent pathway.

BACKGROUND: Prostaglandin D(2) (PGD(2)), a major prostanoid produced by activated mast cells, has long been implicated in allergic diseases. PGD(2) demonstrates its effects through two G-protein-coupled receptors, DP and CRTH2. The PGD(2)/CRTH2 system mediates chemotaxis of eosinophils, basophils, and Th2 cells, which are involved in the induction of allergic inflammation. Although recent studies have shown that the specific receptors for PGD(2), DP, and CRTH2 are expressed in various human tissues, the role of PGD(2) is unknown in human bronchial epithelial cells. In this study, we investigated the expression and function of CRTH2/DP on NCI-H(292) and NHBE cells. METHOD: The CRTH2/DP expression was examined by RT-PCR and flow-cytometric analysis. NCI-H(292) and NHBE cells were cultured in the presence of various stimulants. The resulting supernatants were measured by ELISA. RESULTS: We demonstrated that PGD(2) induced production of IL-8 and GM-CSF in NCI-H(292) and NHBE cells. DK-PGD(2) (CRTH2 agonist) and latanoprost (FP, a prostaglandin F receptor, agonist) failed to augment the production of these cytokines. Pretreatment with ramatroban (CRTH2 antagonist) and AL8810 (FP antagonist) did not reduce the production of these cytokines. The PGD(2)-induced cytokine production was inhibited by pertussis toxin or specific inhibitors for MAP/ERK kinase (PD98059) and p38 MAP kinase (SB202190). CONCLUSION: These results suggest that PGD(2) is a potent inducer of IL-8 and GM-CSF production with MAP/ERK and p38 MAP kinase activation, but this is independent of CRTH2 activation.

Procaterol upregulates peroxisome proliferator-activated receptor-gamma expression in human eosinophils.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates immune reaction. We have previously demonstrated that human eosinophils express PPARgamma and that stimulation with a synthetic agonist for PPARgamma attenuated the factor-induced eosinophil activations. However, the modulator of PPARgamma expression in eosinophils has not yet been studied. In this study, we investigated the effect of procaterol, the synthetic beta2-adrenoceptor agonist widely used as bronchodilators in asthma, on the PPARgamma expression in eosinophils. Purified human peripheral blood eosinophil and the eosinophilic cell line EoL-1 were cultured with procaterol. This was followed by PPARgamma measurement using flow cytometer and quantitative real-time RT-PCR. We observed that PPARgamma was constitutively expressed by EoL-1 and the purified eosinophils and that the therapeutic concentration (10(-9)M) of procaterol markedly enhanced PPARgamma protein expression, which was reversed by the selective beta2-adrenoceptor antagonist ICI-118551. The PPARgamma mRNA expression in EoL-1 and eosinophils was also induced by procaterol. These findings suggest that procaterol could modulate the eosinophil function by increasing the expression of PPARgamma.

Theophylline and dexamethasone induce peroxisome proliferator-activated receptor-gamma expression in human eosinophils.

Eosinophils are major effector cells in allergic diseases including asthma. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates immune reaction. We have previously demonstrated that human eosinophils express PPARgamma and that stimulation with a synthetic agonist for PPARgamma attenuated the factor-induced eosinophil survival and chemotaxis. However, the modulator of the eosinophil PPARgamma expression has not yet been studied. In this study, we investigated the effect of theophylline and dexamethasone (widely used drugs in the treatment of asthma) on PPARgamma expression in eosinophils. Purified human peripheral blood eosinophils were cultured, and therapeutic concentrations of theophylline and dexamethasone were added. Subsequently, PPARgamma was measured using quantitative real-time RT-PCR and flow cytometry. Theophylline and dexamethasone markedly enhanced both mRNA and protein levels of PPARgamma. These findings suggest that the increase in PPARgamma expression on eosinophils may play a role in the anti-inflammatory effects of theophylline and dexamethasone.

Physiological levels of 15-deoxy-Delta12,14-prostaglandin J2 prime eotaxin-induced chemotaxis on human eosinophils through peroxisome proliferator-activated receptor-gamma ligation.

15-Deoxy-Delta12,14-PGJ2 (15d-PGJ2), mainly produced by mast cells, is known as a potent lipid mediator derived from PGD2 in vivo. 15d-PGJ2 was thought to exert its effects on cells exclusively through peroxisome proliferator-activated receptor-gamma (PPARgamma) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), which are both expressed on human eosinophils. However, the physiological role of 15d-PGJ2 remains unclear, because the concentration generated in vivo is generally much lower than that required for its biological functions. In the present study we found that low concentrations (picomolar to low nanomolar) of 15d-PGJ2 and a synthetic PPARgamma agonist markedly enhanced the eosinophil chemotaxis toward eotaxin, and the effect was decreased in a dose-dependent manner. Moreover, at a low concentration (10(-10) M), 15d-PGJ2 and troglitazone primed eotaxin-induced shape change and actin polymerization. These priming effects were completely reversed by a specific PPARgamma antagonist, but were not mimicked by CRTH2 agonist 13,14-dihydro-15-keto-PGD2, suggesting that the effects were mediated through PPARgamma ligation. The effect exerted by 15d-PGJ2 parallels the enhancement of Ca2+ influx, but is not associated with the ERK, p38 MAPK, and NF-kappaB pathways. Furthermore, the time course and treatment of eosinophils with actinomycin D, an inhibitor of gene transcription, indicated that the transcription-independent pathway had a role in this process. PPARgamma might interact with an eotaxin-induced cytosolic signaling pathway, because PPARgamma is located in the eosinophil cytosol. Taken together with current findings, these results suggest that under physiological conditions, 15d-PGJ2 contributes to allergic inflammation through PPARgamma, which plays a role as a biphasic regulator of immune response.

RANTES and eotaxin enhance CD11b and CD18 expression on eosinophils from allergic patients with eosinophilia in the application of whole Blood flow cytometry analysis.

BACKGROUND: C-C chemokines and adhesion molecules expressed on eosinophils play an important role in the pathology of allergic inflammatory disease. C-C chemokines such as eotaxin or RANTES are involved in beta(2) integrin expression on purified eosinophils; so far we have no data on unpurified eosinophils in the peripheral blood. We measured beta(1) and beta(2) integrin activation after stimulation with eotaxin or RANTES in vitro using whole-blood flow-cytometric analysis. METHODS: Heparinized whole blood obtained from allergic patients with eosinophilia or normal subjects was diluted with the same volume of RPMI 1640, and then cells were incubated in the presence or absence of PMA/ionomycin or chemokines for 45 min at 37 degrees C. After hemolyzation with lysing solution, expression of CD11b, CD11a, CD18 and CD49d on eosinophils was measured using flow cytometry. RESULTS: The expression of CD11b, CD11a and CD18 in allergic patients was significantly higher than that in normal subjects. CD11b and CD18 expression showed a significant increase after stimulation with C-C chemokines, which was remarkable in allergic patients. CONCLUSION: Eosinophils in the blood of allergic patients exhibited a higher expression of beta(2) integrins and were more sensitive to RANTES and eotaxin than those of normal subjects.

The synthetic PPARgamma agonist troglitazone inhibits IL-5-induced CD69 upregulation and eosinophil-derived neurotoxin release from eosinophils.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates lipid metabolism. Recently, PPARgamma was reported to be a negative regulator in the immune system. Eosinophils also express PPARgamma, however, the role of PPARgamma in eosinophil functions is not well understood. Surface expression of CD69 and eosinophil-derived neurotoxin (EDN) release are well-known activation markers of eosinophils. We investigated the effect of a PPARgamma agonist on human eosinophil functions such as IL-5-induced CD69 surface expression and EDN release. IL-5 significantly induced eosinophil CD69 surface expression analyzed using flow cytometry and EDN release measured by ELISA. IL-5-induced eosinophil CD69 surface expression and EDN release were significantly inhibited by the synthetic PPARgamma agonist troglitazone, and these effects were reversed by a PPARgamma antagonist. The PPARgamma agonist troglitazone has a potent inhibitory effect on activation and degranulation of eosinophils, and it may be a therapeutic modality for the treatment of allergic diseases.

Peroxisome proliferator-activated receptor gamma regulates eosinophil functions: a new therapeutic target for allergic airway inflammation.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates lipid metabolism and glucose homeostasis. PPARgamma is not only highly expressed in adipose tissue but also in cells involved in the immune system, and it exerts anti-inflammatory activities. We showed that eosinophils, a major inflammatory cell in allergic inflammation, express PPARgamma. PPARgamma negatively modulates eosinophil functions, such as survival, chemotaxis, antibody-dependent cellular cytotoxicity and degranulation. Recently, three independent groups have demonstrated that PPARgamma agonists inhibit airway inflammation in an animal model of asthma. This evidence suggests that PPARgamma agonists may be a new therapeutic modality for the treatment of allergic diseases including asthma.