PPAR-γ agonists, mainly 15d-PGJ2, reduce eosinophil recruitment following allergen challenge

Farnesi-de-Assunção, Thaís Soares; Alves, Claudiney F.; Carregaro, Vanessa; Oliveira, Jhony Robison de; Silva, Carlos A. T. da; Cheraim, Alessandra Bonacini; Cunha, Fernando; Napimoga, Marcelo Henrique

doi:10.1016/j.cellimm.2011.11.010

Cited by 24 publications

(27 citation statements)

References 38 publications

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“…The ω-3-derived resolvins, protectins, and maresins also display potent proresolving actions in a variety of cell types and in in vivo models of inflammatory diseases, including asthma, acute lung injury, and cystic fibrosis (147–151). Moreover, 15d-PGJ 2 resolves chronic eosinophilia following allergen challenge, decreasing airway inflammation (152). Similarly, 15d-PGJ 2 treatment of carrageenan-induced acute lung injury reduces BAL leukocyte and albumin levels in an Nrf2-dependent manner (153).…”

Section: Physiological and Therapeutic Implicationsmentioning

confidence: 99%

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

Delmastro-Greenwood

Freeman

Wendell

2014

Annu. Rev. Physiol.

106

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Unsaturated fatty acids are metabolized to reactive products that can act as pro- or anti-inflammatory signaling mediators. Electrophilic fatty acid species, including nitro- and oxo-containing fatty acids, display salutary anti-inflammatory and metabolic actions. Electrophilicity can be conferred by both enzymatic and oxidative reactions, via the homolytic addition of nitrogen dioxide to a double bond or via the formation of α,β-unsaturated carbonyl and epoxide substituents. The endogenous formation of electrophilic fatty acids is significant and influenced by diet, metabolic, and inflammatory reactions. Transcriptional regulatory proteins and enzymes can sense the redox status of the surrounding environment upon electrophilic fatty acid adduction of functionally significant, nucleophilic cysteines. Through this covalent and often reversible posttranslational modification, gene expression and metabolic responses are induced. At low concentrations, the pleiotropic signaling actions that are regulated by these protein targets suggest that some classes of electrophilic lipids may be useful for treating metabolic and inflammatory diseases.

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Section: Physiological and Therapeutic Implicationsmentioning

confidence: 99%

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

Delmastro-Greenwood

Freeman

Wendell

2014

Annu. Rev. Physiol.

106

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“…Recently, our and other research groups have demonstrated the anti-inflammatory activity of exogenously administered 15d-PGJ 2 (12)(13)(14)(15)(16)(17)(18). However, it has been estimated that .50% of the 15d-PGJ 2 added exogenously to a biological system binds to albumin (11).…”

Section: {‖mentioning

confidence: 99%

Exogenous Administration of 15d-PGJ2–Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Napimoga

Silva

Carregaro

et al. 2012

The Journal of Immunology

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The 15-deoxy-Δ12,14-PG J2 (15d-PGJ2) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nanotechnological formulation as a carrier for 15d-PGJ2, and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D,L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ2. BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 μg/kg 15d-PGJ2-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ2-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 μg/kg 15d-PGJ2-NC had a reduction of CD4+CD25+FOXP3+ cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 μg/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 μg/kg 15d-PGJ2-NC, and high amounts of 15d-PGJ2 were observed in the gingiva. In conclusion, the 15d-PGJ2-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model.

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“…(A) Mice were sensitized by intraperitoneal injection of ovalbumin [28] mixed with aluminum hydroxide on days 0, 7, and 14. Daily OVA intranasal challenge was performed from days 21 to 27.…”

Section: Methodsmentioning

confidence: 99%

Role of Interleukin-17A on the Chemotactic Responses to CCL7 in a Murine Allergic Rhinitis Model

et al. 2017

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BackgroundThe proinflammatory cytokine interleukin (IL)-17A is associated with eosinophil infiltration into the nasal mucosa in a mouse model of ovalbumin-induced allergic rhinitis. Chemotaxis of eosinophils is mediated primarily through C-C chemokine receptor type 3 (CCR3). However, the mechanism underlying the IL-17A-mediated enhancement of eosinophil recruitment via chemoattractants/chemokines remains unknown.ObjectivesIn this study, we assessed the contribution of IL-17A to eosinophil-related inflammation via the CCL7/CCR3 pathway in experimental allergic rhinitis.MethodsIL-17A knockout (KO) and wild-type (WT) BALB/c mice were injected intraperitoneally and challenged intranasally with OVA to induce allergic rhinitis. Various parameters of the allergic response were evaluated, and mRNA and protein levels of CCL7 and CCR3 in nasal tissue and serum were compared between the two groups. The chemotactic response to CCL7 with or without IL-17A in bone marrow-derived eosinophils (bmEos) from BALB/c mice was measured.ResultsIn the allergic rhinitis model, IL-17A deficiency significantly decreased nasal symptoms, serum IgE levels, and eosinophil recruitment to the nasal mucosa. CCL7 and CCR3 mRNA and protein levels were decreased in the nasal mucosa of IL-17A KO mice compared with the WT mice. BmEos showed a significantly increased chemotactic response to -low concentration of CCL7 in the presence of IL-17A compared with its absence.ConclusionThe suppression of nasal inflammation due of IL-17A deficiency in allergic rhinitis is partly responsible for the regulation of CCL7 secretion and eosinophil infiltration, which may be regulated via the CCL7/CCR3 pathway.

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PPAR-γ agonists, mainly 15d-PGJ2, reduce eosinophil recruitment following allergen challenge

Cited by 24 publications

References 38 publications

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

Exogenous Administration of 15d-PGJ2–Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

Role of Interleukin-17A on the Chemotactic Responses to CCL7 in a Murine Allergic Rhinitis Model

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