| BackgroundRhinitis is a common heterogeneous condition that is defined as an inflammation of the nasal mucosa.Allergic rhinitis(AR),the most common allergic inflammation of the airway,affects 10-20% of the population and is a global health issue with an increasing prevalence worldwide.During AR sensitization,inhaled allergens can induce IgE in local and regional drainage lymphoid organs of atopic individuals,combined with high affinity IgE receptors(FcεRI)on the surface of mast cells and basophils accumulated in the nasal mucosa.When exposed to the same allergen,the allergen combines with IgE anchored on the cell surface to activate mast cells and basophils,resulting in the release of inflammatory mediators such as histamine and leukotrienes,which can stimulate The sensory nerve endings and blood vessels of the nasal mucosa excite the parasympathetic nerves,causing symptoms such as itchy nose and sneezing water.In addition,inflammatory mediators such as histamine and leukotriene can further induce inflammatory mediators(leukotriene,prostaglandin),Platelet activating factor,etc.),the inflammatory response continues to increase.In genome-wide association studies,the onset of AR has a certain relationship with genetic-environmental interactions,and AR has genetic susceptibility.Whole-genome association studies have shown at multiple sites such as chromosomes 2q12,5q31,6p21.3,11q13.5 Having a single nucleotide polymorphism may be related to allergic diseases(such as AR),and the microbiome is also crucial in the development of allergic diseases.IgE-mediated type I allergic reaction is the core mechanism of AR pathogenesis,but non-IgE-mediated inflammation is also involved in the development of AR.Allergens with enzymatic activity induce cytokines and chemokines in epithelial cells,promote Th2-related inflammatory responses,and reduce the adhesion of epithelial cell junctions,thereby destroying the barrier function of epithelial cells,promoting dendritic cells and allergies Contact between the original.According to recent research,the nasal mucosa of patients with non-specific constitution produces locally specific IgE,and the allergic nasal irritation test is positive,which is called "local allergic rhinitis",among which common allergens There are mainly mites,pollen,animal fur debris,fungi and insect feces.The current treatment of AR mainly includes environmental control,drug therapy,immunotherapy and health education.The treatment concept is "combination of prevention and treatment,four in one".The main means of environmental control include mite removal agents,nasal mucosa blocking agents,and nasal physiology.Saline cleaning agent,the above method can avoid or reduce the contact between allergens and non-specific irritants to prevent the development of allergic inflammatory reactions,such as seasonal AR caused by pollen and AR caused by pets can be eliminated by allergens and changes Living environment to completely control clinical symptoms.In many cases,environmental allergens,especially indoor inhalable allergens,such as mites and molds,are widely exposed in daily life.Even with the use of mite-removing agents and equipment,they are unavoidable.They can easily cause repeated attacks in AR patients.Infectious rhinitis is a type of rhinitis,often caused by viral or bacterial infections.It usually has an acute onset and a short course of disease,lasting 7-10 days.The nasal symptoms are similar to allergic rhinitis,accompanied by fever,headache,Symptoms such as fatigue,sore limbs and other systemic discomfort,negative allergen test,normal eosinophils,peripheral blood leukocytes and neutrophils increased.Treatment is usually symptomatic antibiotics and antiviral therapy.Although the existing drug treatments are diverse,according to incomplete statistics,one-third to two-thirds of AR patients report poor response.Several studies have shown that cytokines secreted by nasal mucosal epithelial cells such as thymic stromal lymphopoietin(TSLP),interleukin 33(Interleukin-33,IL-33),IL-25,etc.in AR and Viruses play an important role in the development of infectious rhinitis.These cytokines are expected to provide new targets and means for clinical drug treatment at this stage.In this topic,Alternaria alternata(Alternaria)is a common fungal allergen,and is related to respiratory diseases including asthma and allergic rhinitis.At present,many IgE reactive proteins have been identified from Alternaria,so this topic chose it as an allergen-induced in vitro AR model.Polyinosinic: polycytidylic acid [Poly(i:c)] is a synthetic double-stranded RNA that triggers an immune response similar to that observed during viral infections.We can obtain an in vitro model of infectious rhinitis caused by AR and virus through human alveolar epithelial cells induced by Alternaria and Poly(i:c).This study aims to explore the expression of specific proinflammatory cytokines in the potential allergic and inflammatory reactions of nasal mucosa epithelial cells,to provide a theoretical basis for further elucidating the pathogenesis of infectious rhinitis caused by AR and viruses,and for clinical Treatment provides theoretical support and basis.MethodsGenome-wide transcriptome analysis was performed to compare expression of genes coding secreting proteins in Alternaria and Poly(i:c)-treated HNEpCs with vehicle-treated controls.RT-PCR was used to verify gene expression alterations obtained from RNA-seq.Flow cytometry was used to analyze cell cycle progression in Alternaria and Poly(i:c)-treated HNEpCs.Then use SPSS 22.0 for statistical analysis.ResultsAlternaria treatment caused changes of 534 gene expression in HNPECs(P≤0.05),while Poly(i:c)rendered 395 expression-altered genes(P≤0.05).Go analysis revealed markedly activation of multiple anabolic process-related pathways in both Alternaria and Poly(i:c)-treated HNEPCs,including DNA/RNA biosynthesis and transcription,intracellar energy metabolism and cell mitosis.The up-regulated mitotic genes was verified by RT-PCR in Alternaria and Poly(i:c)-treated HNEPCs,and increased proportion of Synthesis(S)phase of cell cycle was induced in HNEPCs by Alternaria or Poly(i:c)treatment(P≤0.05).Moreover,secretory protein-coding gene expression analysis showed unique inflammatory cytokine expression profiles in HNEPCs challenged by Alternaria and Poly(i:c),respectively.Alternaria promoted proinflammatory NAMPT,NUCB2 and GALS9 gene expression in HNEPCs(P≤0.05),while Poly(i:c)potentiated proinflammatory CLCF1,WNT5 A,and CYR61 gene expression(P≤0.05).ConclusionsAlternaria and Poly(i:c)can mediate the inflammatory response of nasal mucosal cells by activating different inflammatory pathways and inflammation-related genes,but they have caused significant upregulation of related genes in the same cellular metabolic pathways,indicating that targeting allergy-specific cytokines maybe an alternative approach for management of allergic rhinitis. |
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