Project description:PM2.5 exposure is closely linked to the exacerbation of asthma. Estrogen related receptor gamma (Esrrg), an orphan nuclear receptor, exerts a crucial role as a transcription factor in various metabolic diseases. Nevertheless, the impacts of Esrrg on PM2.5-triggered asthma aggravation have not been investigated. Herein, ovalbumin (OVA)-induced asthmatic mice were exposed to PM2.5 to establish a mouse model of asthma aggravation by PM2.5. In view of mRNA sequencing, Esrrg was the only member of nuclear receptor superfamily in the up-regulated differentially expressed genes in OVA compared with Naive groups as well as OVA+PM2.5 compared with OVA groups (|log2 (fold change)|>1 and p<0.05). In vivo, adeno-associated virus carrying Esrrg shRNA (AAV-shEsrrg) was applied to silencing Esrrg. In addition, Esrrg activity was suppressed pharmacologically with an inverse agonist GSK5182. Either AAV-shEsrrg or GSK5182 ameliorated airway inflammation in the PM2.5-aggravated asthmatic mice. In vitro, isolated mouse primary tracheobronchial epithelial cells (MTEC) from mice were identified by detecting cytokeratin 7-positive cells. The treatment of adenovirus vector with shEsrrg or GSK5182 mitigated the cell damage induced by PM2.5. Notably, phosphodiesterase 3B (Pde3b) expression was declined by Esrrg inhibition in vivo and in vitro. Dual luciferase reporter and ChIP-PCR assays showed the binding of Esrrg to the Pde3b promoter. Taken together, these results revealed that Esrrg inhibition alleviated airway inflammation in the PM2.5-deteriorated asthmatic mouse model and prevented PM2.5-driven MTEC injury through binding to the Pde3b promoter, which might contribute to further study the therapy of PM2.5-aggravated asthma.
Project description:To better understand the molecular processes of nebulized Hypo-Evs on asthma intervention, OVA-induced chronic asthma model were established (OVA group), and a therapeutic regimen was instigated by inhaling Hypo-EVs four times (Hypo-EVs group) . Then a global RNA sequencing of mouse lung from the OVA and Hypo-EVs groups was performed.
Project description:We examined the effect of PGE receptor EP3 subtype on mouse OVA-induced asthma model. We treat EP3 agonist 3h after OVA challenge. After 24 h of 3rd OVA challenge, whole lung was isolated and the gene expression change was determined.
Project description:CpG-oligodeoxynucleotides (CpG-ODNs) constitute an attractive alternative for asthma treatment. We found that free feeding of an ODNcap (a CpG-ODN-embedded particle) -containing feed (ODNcap-F) prophylactically attenuates allergic airway inflammation, hyperresponsiveness, and goblet cell hyperplasia in an ovalbumin (OVA) -induced asthma model. To seek the suppressive mechanism of action of ODNcap-F in OVA-induced airway insults, we analyzed the lung transcriptome using DNA microarray analysis.
Project description:To investigate the role of γ-glutamyltranspeptidase in severe asthma, we established an OVA/ LPS-induced asthma model. Inflammation analysis and second-generation sequencing revealed the mechanism by which inhibition of γ-glutamyltranspeptidase inhibited LPS-induced asthma exacerbation in mice.
Project description:Asthma bronchiale is an inflammatory disease of the respiratory airways and a major factor of increasing health care costs worldwide. The molecular actors leading to asthma are not fully understood and require further investigation. The aim of this study was to monitor the proteome during asthma development from early inflammatory to late fibrotic stages. A time-course-based ovalbumin (OVA) mouse model was applied to establish an asthma phenotype and the lung proteome was analysed at four time points during asthma development (0 weeks = control, 5 weeks, 8 weeks and 12 weeks of OVA treatment).
Project description:We examined the effect of PGE receptor EP3 subtype on mouse OVA-induced asthma model. We treat EP3 agonist 3h after OVA challenge. After 24 h of 3rd OVA challenge, whole lung was isolated and the gene expression change was determined. Keywords: other
Project description:Immunoglobulin (Ig) E-mediated activation of mast cells and basophils underlies allergic diseases such as asthma. Histamine-releasing factor (HRF), also known as translationally controlled tumor protein (TCTP) and fortilin, is a highly conserved protein with both intracellular and extracellular functions. Secreted HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF is found in nasal, skin blister and bronchoalveolar lavage (BAL) fluids during late-phase allergic reactions (LPRs), which implicates HRF in the LPR and chronic allergic inflammation. Here we identify a subset of IgE and IgG antibodies as HRF-interacting molecules. HRF can exist as a dimer and bind to immunoglobulins (Igs) via interactions of its N-terminal and internal regions with the Fab region of Igs. Therefore, HRF together with HRF-reactive IgE can activate mast cells in vitro. The Ig-interacting HRF peptides that block HRF-Ig interactions can inhibit IgE+HRF-induced mast cell activation and in vivo cutaneous anaphylaxis and airway inflammation. Intranasally administered HRF can recruit inflammatory immune cells to the lung in naïve mice in a mast cell- and Fc receptor-dependent manner. These results strongly suggest the proinflammatory role of HRF in asthma and skin immediate hypersensitivity. A total of 6 samples were analyzed; wild type C57BL/6, FcRg KO and FceRIa KO mice were challenged with PBS (control) or mouse histamien-releasing factor