Pioglitazone Attenuates Allergic Inflammation and Induces Production of Regulatory T Lymphocytes

Molecular Medicine Reports

et al. 2017

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Peroxisome proliferator-activated receptor gamma (PPAR γ), is important in the immunoregulation of the allergic response. Mast cells are the most important inflammatory cells in immediate hypersensitivity and allergic diseases. However, there is limited information regarding the effects of PPAR γ on mast cell maturation. In the present study, mouse bone marrow-derived mast cells (BMMCs) were cultured in interleukin (IL)-3 and stem cell factor (SCF), in the presence or absence of the PPAR γ agonist, pioglitazone (PIO). The expression levels of the tyrosine kinase receptor CD117 and the high affinity IgE receptor FcεRI α, were assessed by flow cytometry, cell viability was assessed by Alamar-Blue assay and histamine release was determined by measuring the activity of β-hexosaminidase. IL-3 and SCF are required for the development of mast cells in vitro. PIO dose-dependently inhibited the expression of CD117 and FcεRI α, and the maturation of BMMCs. Treatment with PIO additionally inhibited the formation of granules and reduced the expression of β-hexosaminidase. In addition, reverse transcription-polymerase chain reaction analysis revealed that BMMCs treated with PIO expressed a lower level of mast cell protease (MCP)-6 mRNA and PIO treatment enhanced the level of PPAR γ mRNA. Furthermore, PIO induced mast cell progenitor apoptosis. PPAR γ agonists may maintain mast cell homeostasis by inhibiting maturation of their precursors. The inhibitory effects of PPAR γ agonists include suppression of the activation of mast cells and a decrease in mast cell function in the inflammatory response. Therefore, PPAR γ agonists may serve as effective anti-inflammatory reagents in the treatment of allergic reactions.

Section: Discussionsupporting

confidence: 90%

“…We previously reported that PPAR γ agonist attenuated allergic inflammation in a mouse model of allergic rhinitis ( 21 ). PIO is the effective agent in suppressing allergic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ agonist suppresses mast cell maturation and induces apoptosis

Fang

Molecular Medicine Reports

et al. 2017

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“…The dose of pioglitazone was chosen based on published reports and modified as a result of results from our laboratory. 24, 25 …”

Section: Materials and Methods Or Experimental Proceduresmentioning

confidence: 99%

Pioglitazone reduces inflammation through inhibition of NF-κB in polymicrobial sepsis

et al. 2013

The insulin sensitizing thiazolidinedione drugs, rosiglitazone and pioglitazone are specific peroxisome proliferator-activated receptor-gamma (PPARγ) agonists and reduce pro-inflammatory responses in patients with type 2 diabetes and coronary artery disease and may be beneficial in sepsis. Sepsis was induced in 8–10 wk old C57BL/6 mice by cecal ligation and puncture (CLP) with a 22g double puncture technique. Mice received intraperitoneal injection of vehicle (DMSO:PBS) or pioglitazone (20mg/kg) at 1h and 6h after CLP and were sacrificed at various timepoints. In sepsis, vehicle-treated mice had hypoglycemia, increased lung injury and increased lung neutrophil infiltration. Pro-inflammatory plasma cytokines were increased but the plasma adipokine, adiponectin, was decreased in vehicle-treated septic mice. This corresponded with inhibitor κB (IκBα) protein degradation and an increase in NF-κB activity in lung. Pioglitazone treatment improved plasma glucose and adiponectin levels and decreased pro-inflammatory cytokines. Lung IκBα protein expression increased and corresponded with a decrease in nuclear factor kappa-B (NF-κB) activity in the lung from pioglitazone treated mice. Pioglitazone reduces the inflammatory response in polymicrobial sepsis in part through inhibition of NF-κB and may be a novel therapy in sepsis.

“…CD4 + Foxp3 + T regulatory cells (Tregs) are pivotal in the maintenance of self‐tolerance and immune homeostasis. They are known to exert therapeutic effects on autoimmune diseases, allergy, and allograft rejection in murine models and human patients . At least 2 subtypes of Tregs have been described: thymically derived natural Tregs (nTregs), and inducible Tregs (iTregs) generated peripherally from CD4 + CD25 − T effector cells (Teffs).…”

mentioning

confidence: 99%

Dexamethasone suppresses allergic rhinitis and amplifies CD4⁺Foxp3⁺ regulatory T cells in vitro

Cui

Int Forum Allergy Rhinol

et al. 2015

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