ovalbumin and imperatorin

Imperatorin is a furanocoumarin derivative and an effective ingredient in several Chinese medicinal herbs. It has favorable expectorant, analgesic, and anti-inflammatory effects. In this study, we investigated whether imperatorin has protective effects against

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Dermatophagoides pteronyssinus; Disease Models, Animal; Eosine Yellowish-(YS); Expectorants; Furocoumarins; Hematoxylin; Immunoglobulin E; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

In this study, we investigated the role and mechanism of imperatorin (IMP) in chronic inflammation and airway remodeling. The levels of TNF-α, IL-1β, IL-6, IL-8, VEGF, α-SMA, and ROS were detected by ELISA, immunohistochemistry (IHC), immunofluorescence, and Western blot. In addition, we evaluated the effect of IMP on MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 signaling pathways. IMP treatment obviously attenuated the production of inflammatory cytokines and inflammatory cells in bronchoalveolar lavage fluid of OVA-induced airway remodeling model. Meanwhile, it significantly inhibited inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition, VEGF production, α-SMA, and ROS expression. Our study has shown that IMP could regulate the signaling pathways including MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 to release the inflammatory responses. IMP might attenuate airway remodeling by the down-regulation of Nrf2/HO-1/ROS/PI3K/Akt, Nrf2/HO-1/ROS/MAPK, and Nrf2/HO-1/ROS/NF-κB signaling pathways.

Topics: Airway Remodeling; Animals; Asthma; Cell Line; Cytokines; Disease Models, Animal; Female; Furocoumarins; Heme Oxygenase-1; Membrane Proteins; Mice; Mice, Inbred BALB C; Myocytes, Smooth Muscle; NF-E2-Related Factor 2; Ovalbumin; Reactive Oxygen Species; Signal Transduction

Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and possesses various biological activities. Herein, we investigated the antiallergic effects of imperatorin in asthmatic mice and explored the immunomodulatory actions of imperatorin on immune cells. We used a murine model of ovalbumin (OVA)-induced asthma to evaluate the therapeutic potential of imperatorin. Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to clarify whether imperatorin exerts an antiallergic effect through altering the ability of DCs to regulate T cells. Oral administration of imperatorin to OVA-sensitized and -challenged mice decreased serum OVA-specific immunoglobulin E (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated airway inflammation in a dose-dependent manner. Notably, secretions of Th2 cytokines and chemokines were reduced, and numbers of interleukin (IL)-10-producing regulatory T cells (Tregs) increased in imperatorin-treated mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared to fully mature DCs, imperatorin-treated DCs expressed high levels of the inducible costimulatory ligand (ICOSL) and Jagged1 molecules, and had the regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell proliferation and cytokine production. Imperatorin may possess therapeutic potential against Th2-mediated allergic asthma not only via stimulating DC induction of Tregs but also via direct inhibition of Th2 cell activation. These findings provide new insights into how imperatorin affects the Th2 immune response and the development of imperatorin as a Treg-type immunomodulatory agent to treat allergic asthma.

Topics: Animals; Anti-Allergic Agents; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Cell Proliferation; Cells, Cultured; Dendritic Cells; Disease Models, Animal; Female; Furocoumarins; Immunoglobulin E; Inducible T-Cell Co-Stimulator Ligand; Interleukin-10; Jagged-1 Protein; Lung; Lymphocyte Activation; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Phenotype; Signal Transduction; T-Lymphocytes, Regulatory; Th2 Cells; Time Factors

Because imperatorin (IPT), the furanocoumarins exhibits anti-inflammatory activity, we reasoned that IPT might modulate the allergic rhinitis (AR). The aim of this study was to analyze the regulation of AR by IPT. Here, we show the effect and mechanism of IPT in an ovalbumin (OVA)-induced AR model. The number of rubs after the OVA challenge in the OVA-sensitized mice was significantly higher than that in the OVA-unsensitized mice. The increased number of rubs was inhibited by the oral administration of IPT. The increased levels of IgE and histamine in the OVA-sensitized mice were reduced by IPT administration. The levels of interferon-γ were enhanced, whereas the levels of interleukin (IL)-4 were reduced on the spleen tissue of the IPT-administered AR mice. Protein levels of IL-1β, macrophage inflammatory protein-2, intercellular adhesion molecule-1, and cyclooxygenase-2 were reduced by IPT administration in the nasal mucosa of the OVA-sensitized mice. In the IPT-administered mice, the number of eosinophils and mast cells infiltration increased by OVA-sensitization were also decreased. In addition, IPT inhibited caspase-1 activity in the same nasal mucosa tissue. In activated human mast cells, the receptor-interacting protein 2 (RIP2), IκB kinase (IKK)-β, nuclear factor-κB (NF-κB)/RelA, and caspase-1 activation were increased, but increased RIP2, IKK-β, NF-κB/RelA, and caspase-1 activation were inhibited by the treatment of IPT. In addition, IPT inhibited caspase-1 activity and IL-1β production in IgE-stimulated bone marrow-derived mast cells. We can conclude that IPT exerts significant effects by regulating of caspase-1 activation in AR animal and in vitro models.

Topics: Animals; Blotting, Western; Bone Marrow Cells; Caspase 1; Caspase Inhibitors; Cell Line; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Furocoumarins; Histamine; Histamine Release; Humans; I-kappa B Proteins; Inflammation; Mast Cells; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Peroxidase; Receptor-Interacting Protein Serine-Threonine Kinase 2; Receptor-Interacting Protein Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic, Perennial