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Effects of lentivirus-mediated CCR3 RNA interference on the function of mast cells of allergic rhinitis in mice
- Source :
- International immunopharmacology. 78
- Publication Year :
- 2019
-
Abstract
- The CC chemokine receptor 3 (CCR3) expressed by eosinophils, mast cells and Th2 cells is closely related to allergic diseases. The objective of this study was to explore whether silencing of CCR3 with short hairpin RNAs (shRNAs) delivered by a lentiviral vector could impact the function of mast cells in a murine model of allergic rhinitis (AR) in vivo. The murine model of allergic rhinitis (AR) inducing by ovalbumin (OVA) was constructed, and the BALB/c mice were divided into normal control group, AR group, controlshRNA treated group and lentiviral CCR3-shRNA treated group. The recombinant lentivirus vectors which express a short hairpin RNA (shRNA) targeting the CCR3 were dropped into the nasal cavity of OVA-sensitized mice before the challenges. Real-time fluorescence quantitative PCR and western blotting were performed to observe inhibitory effect of CCR3 gene. Nasal symptoms of mice and OVA-specific IgE in each group were assessed. Concentrations of histamine, tryptase and Prostaglandin D2 (PGD2) in bone marrow, peripheral blood and nasal mucosa were analyzed. Furthermore, histological analysis and electron microscopy analysis were applied to detect the histology changes of nasal mucosa and the infiltration of mast cells in nasal mucosa. The results showed that administration of CCR3shRNA could effectively inhibit the expression of the CCR3 gene in bone marrow, peripheral blood and nasal mucosa, which reduced the nasal symptoms, the level of OVA-specific IgE, the inflammatory cells and mast cells infiltration into nasal cavity, and relieved the histopathological changes of nasal mucosa. In addition, intervention of CCR3shRNA could reduce the levels of the histamine, tryptase and PGD2 in bone marrow, peripheral blood and nasal mucosa. These results suggest that inhibition of CCR3 gene expression by shRNAs lentiviral vectors can effectively attenuate migration, infiltration and degranulation of mast cells in local tissues and alleviate the inflammation of allergic rhinitis mice.
- Subjects :
- 0301 basic medicine
Nasal cavity
Male
Ovalbumin
Receptors, CCR3
Immunology
Mucous membrane of nose
Tryptase
Aluminum Hydroxide
Immunoglobulin E
Cell Degranulation
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Adjuvants, Immunologic
Bone Marrow
Cell Movement
medicine
Immunology and Allergy
Animals
Humans
Mast Cells
RNA, Small Interfering
Pharmacology
biology
business.industry
Lentivirus
Degranulation
respiratory system
Rhinitis, Allergic
Disease Models, Animal
Microscopy, Electron
Nasal Mucosa
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
biology.protein
RNA Interference
Prostaglandin D2
Bone marrow
business
Histamine
Subjects
Details
- ISSN :
- 18781705
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- International immunopharmacology
- Accession number :
- edsair.doi.dedup.....9c1a8b873a3a9b1af984fdeec6688d0c