CCR3 gene knockout in bone marrow cells ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing airway inflammatory cell infiltration and Th2 cytokines expression in mice model

Dai, MeiNa; Zhu, Xinhua; Yu, Juan; Yuan, JiaSheng; Zhu, Yv; Bao, Youwei; Yong, XiaoZhuang

doi:10.1016/j.intimp.2021.108509

Cited by 14 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemokines are small molecule-scale cytokines that recruit leukocyte subsets under steady-state and pathological conditions; signaling pathways are activated by their binding to receptors on the cell surface and are involved in chronic in ammatory and autoimmune diseases. Multiple studies have shown that knockdown of the chemokine receptor CCR3 reduces eosinophilic in ammation and the Th2 immune response in AR [36][37][38]. In summary, our ndings are in accordance with all of the above studies.…”

Section: Discussionsupporting

confidence: 91%

Identification and analysis of lipid metabolism-related genes in allergic rhinitis

Tao

Zhu

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background:Studies have shown that the lipid metabolism mediator leukotriene is associated with the pathogenesis of allergic rhinitis (AR). The aim of this study was to identify key lipid metabolism-related genes (LMRGs) related to the diagnosis and treatment of AR. Material and methods: AR-related expression datasets (GSE75011, GSE46171) were downloaded through the Gene Expression Omnibus (GEO) database. First, weighted gene coexpression network analysis (WGCNA) was used to get AR-related genes (ARRGs). Next, between control and AR guoups in GSE75011, differentially expressed genes (DEGs) were screened, and DEGs were intersected with LMRGs to obtain lipid metabolism-related differentially expressed genes (LMR DEGs). Protein‒protein interaction (PPI) networks were constructed for these LMR DEGs. Hub genes were then identified through stress, radiality, closeness and edge percolated component (EPC) analysis and intersected with the ARRGs to obtain candidate genes. Biomarkers with diagnostic value were screened via receiver operating characteristic (ROC) curves.Differential immune cells screened between control and AR groups were then assessed for correlation with the diagnostic genes, and clinical correlation analysis and enrichment analysis were performed. Finally, reverse transcription-polymerase chain reaction(RT‒qPCR) was made on blood samples from control and AR patients to validate these identified diagnostic genes. Results: 73 LMR DEGs were obtained, which were involved in biological processes such as metabolism of lipids and lipid biosynthetic processes. Sixty-six ARRGs and 22 hub genes were intersected to obtain four candidate genes. Three diagnostic genes (LPCAT1, SGPP1, SMARCD3) with diagnostic value were screened according to the AUC > 0.7, with markedly variant between control and AR groups. In addition, two immune cells, regulatory T cells (TReg) and T follicular helper cells (TFH), were marked variations between control and AR groups, and SMARCD3 was significantly associated with TFH. Moreover, SMARCD3 was relevant to immue-related pathways, and correlated significantly with clinical characteristics (age and sex). Finally, RT‒qPCR results indicated that changes in the expression of LPCAT1 and SMARCD3 between control and AR groups were consistent with the GSE75011 and GSE46171. Conclusion: LPCAT1, SGPP1 and SMARCD3 might be used as biomarkers for AR.

show abstract

Section: Discussionsupporting

confidence: 91%

Identification and analysis of lipid metabolism-related genes in allergic rhinitis

Tao

Zhu

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In the same context, interrupting CCR3 by anti-CCR3 Ab serves as a key therapeutic intervention to attenuate mucus overproduction and airway remodeling involved in the pathogenesis and progression of asthma [27]. The latest studies showing CCR3 knockout to alleviate inflammatory cell infiltration in murine airways of combined allergic rhinitis and asthma syndrome support our thesis in the same vein [28]. In opposition to these findings, randomized clinical trial on asthma and eosinophilic bronchitis demonstrated that oral CCR3 antagonist failed to improve airway eosinophilia and clinical indicator of asthma severity (FEV1) [29].…”

Section: Discussionmentioning

confidence: 63%

C-C Motif Chemokine Receptor 3-Mediated Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Signaling: Promising Targets for Human Airway Epithelial Mucin 5AC Induction by Eotaxin-2 and Eotaxin-3

Choi

et al. 2023

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Introduction: Eotaxin-2 and -3 of the C-C chemokine subfamily function as potent chemoattractant factors for eosinophil recruitment and various immune responses in allergic and inflammatory airway diseases. Mucin 5AC (MUC5AC), a major gel-forming secretory mucin, is overexpressed in airway inflammation. However, the association between mucin secretion and eotaxin-2/3 expression in the upper and lower airway epithelial cells has not been fully elucidated. Therefore, in this study, we investigated the effects of eotaxin-2/3 on MUC5AC expression and its potential signaling mediators. Methods: We analyzed the effects of eotaxin-2 and -3 on NCI-H292 human airway epithelial cells and primary human nasal epithelial cells (HNEpCs) via reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Along with immunoblot analyses with specific inhibitors and small interfering RNA (siRNA), we explored the signaling pathway involved in MUC5AC expression following eotaxin-2/3 treatment. Results: In HCI-H292 cells, eotaxin-2/3 activated the mRNA expression and protein production of MUC5AC. A specific inhibitor of C-C motif chemokine receptor 3 (CCR3), SB328437, suppressed eotaxin-2/3-induced MUC5AC expression at both the mRNA and protein levels. Eotaxin-2/3 induced the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and p38, whereas pretreatment with a CCR3 inhibitor significantly attenuated this effect. Induction of MUC5AC expression with eotaxin-2/3 was decreased by U0126 and SB203580, specific inhibitors of ERK1/2 and p38 mitogen-activated protein kinase (MAPK), respectively. In addition, cell transfection with ERK1/2 and p38 siRNAs inhibited eotaxin-2/3-induced MUC5AC expression. Moreover, specific inhibitors (SB328437, U0126, and SB203580) attenuated eotaxin-2/3-induced MUC5AC expression in HNEpCs. Conclusion: Our results imply that CCR3-mediated ERK1/2 and p38 MAPK are involved in the signal transduction of eotaxin-2/3-induced MUC5AC overexpression.

show abstract

“…6,7 Afterward, inflammatory mediators stimulate the nasal mucosal epithelium to secrete chemokine eotaxin, which combines with CC chemokine receptor 3 (CCR3) highly expressed on the surface of mast cells and eosinophils (EOS), inducing the recruitment and infiltration of inflammatory cells in the nasal mucosa and further aggravating the inflammatory reaction in the late phase (Figure S1). 8,9 Common treatments includes allergen avoidance, drug treatment (antihistamines, decongestants, glucocorticoids, etc. ), specific immunotherapy, and surgical intervention.…”

Section: Introductionmentioning

confidence: 99%

“…AR is hardly completely cured, usually persists throughout life, and seriously affects people’s quality of life worldwide. , In the early stage of AR, mast cells release histamine, leukotrienes, and other inflammatory mediators, which play a key role in the induction and maintenance of typical allergic symptoms. , Afterward, inflammatory mediators stimulate the nasal mucosal epithelium to secrete chemokine eotaxin, which combines with CC chemokine receptor 3 (CCR3) highly expressed on the surface of mast cells and eosinophils (EOS), inducing the recruitment and infiltration of inflammatory cells in the nasal mucosa and further aggravating the inflammatory reaction in the late phase (Figure S1). , Common treatments includes allergen avoidance, drug treatment (antihistamines, decongestants, glucocorticoids, etc. ), specific immunotherapy, and surgical intervention. − Among these applications, nasal administration is especially suitable because of rapid absorption of drugs and low required dosage. , However, nasal drug administration usually suffers from mucosa irritants via direct contact, poor permeability, and short residence time in the nasal cavity, which were not beneficial to eliminate rhinitis symptoms. , Therefore, there are urgent demands to develop effective nasal delivery strategies with augmented antiallergic therapeutic efficacy and reduced side effects.…”

Section: Introductionmentioning

confidence: 99%

Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis

Teng,

Yang,

Chen

et al. 2023

ACS Nano

View full text Add to dashboard Cite

CCR3 gene knockout in bone marrow cells ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing airway inflammatory cell infiltration and Th2 cytokines expression in mice model

Cited by 14 publications

References 34 publications

Identification and analysis of lipid metabolism-related genes in allergic rhinitis

Identification and analysis of lipid metabolism-related genes in allergic rhinitis

C-C Motif Chemokine Receptor 3-Mediated Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Signaling: Promising Targets for Human Airway Epithelial Mucin 5AC Induction by Eotaxin-2 and Eotaxin-3

Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis

Contact Info

Product

Resources

About