Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma

PURPOSE: Asthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms. METHODS: A total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics (P < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics (P = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma (P < 0.05 for each). CONCLUSIONS: These findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.

Clinical significance of asthma predictive index, Etoaxin, interleukin-4, interferon-γ in infants with recurrent wheezing / 中华实用儿科临床杂志

Objective@#To investigate the clinical significance of asthma prediction index (API), Eotaxin(Eot), interleukin-4 (IL-4), interferon-γ (IFN-γ), eosinophil (Eos) in predicting recurrent wheezing in infants.@*Methods@#Ninety-six infants with first wheezing attack due to bronchiolitis from April 2015 to April 2016 at the Department of Pediatrics, the Second Hospital of Tianjin Medical University were selected.The medical history and other clinical data were collected, and the peripheral blood samples were collected to detect Eot, IL-4, IFN-γ, Eos count and serum specific immunoglobulin E(sIgE). Then all infants were followed up by telephone until 2-year-old to find whether recurrent wheezing attack occurred and then API was calculated.According to the recurrent wheezing times during the follow-up, they were divided into 2 groups: the observation group (recurrent attacks≥2 times, 33 cases) and the control group (no recurrent wheezing during follow-up, 60 cases). The infants in the observation group were divided into the API positive group (18 cases) and the API negative group (14 cases) according to API.The differences in clinical data and peripheral blood indexes were analyzed by independent sample t test for measuring data and χ2 test for counting data.@*Results@#Thirty-three cases (35.48%) infants in the study had recurrent wheezing attacks within 2 years followed by bronchiolitis.The average age of the recurrent wheezing attack was (13.59±5.89) months.Compared with the control group, the levels of serum Eot[(135.45±44.45) ng/L vs.(110.91±22.50) ng/L, t=3.44, P<0.05], IL-4[(58.56±43.55) ng/L vs.(34.91±12.18) ng/L, t=3.78, P<0.05] and peripheral blood Eos proportion(0.034 0±0.025 6 vs.0.003 3±0.006 4, t=4.56, P<0.05) increased in the observation group, and the differences were statistically significant.The food allergy history [18.18%(6/33 cases) vs.5.00%(3/60 cases), χ2=4.23, P<0.05]and the positive proportion of sIgE allergens[38.46%(10/26 cases) vs.9.09%(2/22 cases), χ2=5.48, P<0.05] increased, and the differences were statistically significant.There was no difference between the 2 groups in IFN-γ level (P>0.05). The level of serum Eot [(146.59±59.35) ng/L vs.(114.14±13.60) ng/L, t=3.71, P<0.05], airway sIgE[45.00%(9/20 cases) vs.0(0/6 case), χ2=4.13, P<0.05]and food allergens sIgE [50.0%(10/20 cases) vs.0(0/6 case), χ2=4.88, P<0.05)] in the API positive group was higher than that in the API negative group, and the differences were statistically significant.@*Conclusions@#The elevated serum Eot levels during the first asthmatic attack of bronchiolitis in infants and food sIgE positive levels suggest an increased risk of recurrent wheezing, and the elevated serum Eot levels and sIgE positive levels are associated with API positive levels.

The association between polymorphisms of Eotaxin gene and the allergy to cow's milk protein in infants / 中华实用儿科临床杂志

Objective To assess the association between-426C＞T,-384A＞G,+ 67G＞A polymorphisms in Eotaxin gene and cow's milk protein allergy (CMPA) in infants.Methods One hundred and six patients with CMPA who were hospitalized at Children's Hospital Affiliated to Nanjing Medical University from July 2014 to July 2015 were selected as CMPA group,and 124 healthy infants chosen from Ninghai Road Community Health Service Centers at the same time were selected as healthy control group,and the serum levels of Eotaxin in 2 groups were measured by enzyme-linked immunosorbent assay (ELISA),polymerase chain reaction (PCR) and DNA direct sequencing technology were used to detect the genotypes for single nucleotide polymorphisms (SNPs) of-426C ＞ T,-384A ＞ G,and + 67G ＞ A in Eotaxin gene.The association between the SNPs of-426C ＞ T,-384A ＞ G,and + 67G ＞ A in Eotaxin gene and CMPA,the peripheral blood eosinophil counts,serum Eotaxin levels,and serum total immunoglobulin E levels were analyzed.Results For-426C ＞ T,the frequency of each genotype of the CMPA group was CC,CT,TF (79.25％,19.81％,0.94％),while the frequency of each genotype of the healthy control group was CC,CT,TT(88.71％,8.06％,3.23％).There was a significant difference in the genotype frequency in-426C ＞ T between the CMPA group and the healthy control group (x2 =7.83,P ＜ 0.05).The individuals with heterozygous genotype(CT) had a 1.75-fold increased risk of developing CMPA compared with the individuals with wild-type genotype (CC) [odds ratio (OR) =2.75,95％ confidence interval(CI):1.23-6.15,P ＜ 0.05].For position + 67G ＞ A,CMPA patients with a genotype including variant nucleotide had lower peripheral blood eosinophil counts [(0.48 ± 0.06) × 109/L] and serum Eotaxin levels [(157.67 ± 12.72) ng/L] than those with wild-type genotype [(0.85 ± 0.09) × 109/L,(286.96 ± 33.23) ng/L] (F =10.30,5.75,all P ＜ 0.05).Conclusions Polymorphism of the Eotaxin gene (-426C ＞ T) was associated with the susceptibility to CMPA.Polymorphism of the Eotaxin gene(+ 67G ＞ A) was related to the blood eosinophil counts and the serum Eotaxin levels in children with CMPA.

Impact of eotaxin-3 gene polymorphisms on inhaled corticosteroids in patients with bronchial asthma / 重庆医学

Objective To investigate the impact of eotaxin-3 gene polymorphisms on the clinical effect of inhaled corticosteroids (ICS) to provide clinical basis for eotaxin-3 as the target spot for treating bronchial asthma.Methods One hundred and ninety-six cases of asthma and 196 cases as controls were selected from the outpatients and inpatients in our hospital.Peripheral blood samples were collected from the asthma patients and normal controls.PCR-RFLP was adopted to detect the genotypes of eotaxin-3 +2497T＞G and-+-77C＞T.The response of ICS treatment and the change situation of ACT scores were compared among asthmatic patients with various genotypes.Results Peripheral blood eosinophil(EOS) counts,EOS proportion and total IgE in the patients with TG genotype at+2497 locus were significantly decreased compared with those in the patients with TT genotype,the difference was statistically significant(P＜0.05).The level of PD20 in asthmatic patients with TG genotype was significantly higher than that in the patients with TT genotype,the difference was statistically significant[(0.07-±-0.03)mg vs.(0.03 ± 0.01)mg,t=2.45,P=0.048];whereas the above indicators had no statistical difference among 3 kinds of +-77 genotypes.During ICS treatment process in the patients with TT genotype at +-2497 locus,the FEV1％,PD20 value and ACT scores were significantly improved compared with those in the patients with TG genotype,the difference was statistically significant(P＜0.01).Conclusion The asthmatic patients with TT genotype at +-2497 locus were more sensitive to ICS treatment,regular ICS treatment can significantly improve the lung function and clinical symptom score in these patients.

Impact of eotaxin-3 gene polymorphisms on inhaled corticosteroids in patients with bronchial asthma / 重庆医学

Objective To investigate the impact of eotaxin-3 gene polymorphisms on the clinical effect of inhaled corticosteroids (ICS) to provide clinical basis for eotaxin-3 as the target spot for treating bronchial asthma.Methods One hundred and ninety-six cases of asthma and 196 cases as controls were selected from the outpatients and inpatients in our hospital.Peripheral blood samples were collected from the asthma patients and normal controls.PCR-RFLP was adopted to detect the genotypes of eotaxin-3 +2497T＞G and-+-77C＞T.The response of ICS treatment and the change situation of ACT scores were compared among asthmatic patients with various genotypes.Results Peripheral blood eosinophil(EOS) counts,EOS proportion and total IgE in the patients with TG genotype at+2497 locus were significantly decreased compared with those in the patients with TT genotype,the difference was statistically significant(P＜0.05).The level of PD20 in asthmatic patients with TG genotype was significantly higher than that in the patients with TT genotype,the difference was statistically significant[(0.07-±-0.03)mg vs.(0.03 ± 0.01)mg,t=2.45,P=0.048];whereas the above indicators had no statistical difference among 3 kinds of +-77 genotypes.During ICS treatment process in the patients with TT genotype at +-2497 locus,the FEV1％,PD20 value and ACT scores were significantly improved compared with those in the patients with TG genotype,the difference was statistically significant(P＜0.01).Conclusion The asthmatic patients with TT genotype at +-2497 locus were more sensitive to ICS treatment,regular ICS treatment can significantly improve the lung function and clinical symptom score in these patients.

Correlations of plasma eotaxin-2, sTNFR Ⅱ and other cytokines levels with the status of metabolic syndrome in type 2 diabetic nephropathy patients treated with maintenance hemodialysis / 临床检验杂志

Objective To investigate the correlations of plasma eotaxin-2,soluble tumor necrosis factor receptor(sTNFR) Ⅱ and other cytokines levels with the status of metabolic syndrome(MS) in type 2 diabetic nephropathy (DN) patients treated with maintenance hemodialysis(MHD).Methods Thirty type 2 DN patients with stable pathogenetic conditions and MHD treatment for more than 3 months,thirty newly diagnosed and untreated type 2 diabetes(T2D) patients and thirty healthy volunteers were enrolled in the study.The MS related markers,including blood pressure,waist circumference,body mass index,triglyceride(TG),high density lipoprotein cholesterol(HDL-C),fasting blood glucose (FBG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C) and C reactive protein(CRP),were determined.The expression levels of 40 cytokines were detected with the AAH-INF-G3 antibody microarray,and their correlations with MS related markers were analyzed by the Pearson method.Results The incidence rates of MS in DN patients with MHD and T2D patients were 88.89％ and 33.33％,respectively.Compared with T2D patients and healthy controls,the DN patients had more MS related markers,higher waist circumference and lower body mass index,and their plasma eotaxin-2,I-309 and sTNFR Ⅰ / Ⅱ levels increased significantly.Pearson correlation analysis showed that plasma eotaxin-2 and I-309 levels were positively related to MS risk factors such as TG,FBG and diastolic blood pressure(DBP) levels.Plasma sTNFR Ⅱ and I-309 levels were significantly positively correlated with plasma CRP levels.Conclusion A micro inflammatory state exists in type 2 DN patients with MHD.Abnormal glycolipid metabolism may influence on the immunologic and physiological state of human body,and then form the micro inflammatory state.Eotaxin-2 and I-309 may participate in this chronic and persistent process and further induce renal damage by upregulating sTNFR Ⅰ / Ⅱ levels,which may result in the formation of MS state in type 2 DN patients with MHD.

Correlations of Eotaxin-1, rheumatoid factor and anti-cyclic citrullinated peptide antibody with the activity of rheumatoid arthritis / 临床检验杂志

Objective To investigate the correlations of Eotaxin-1,rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody with the activity of rheumatoid arthritis (RA).Methods A total of 58 patients with early RA,46 patients without RA and 53 healthy controls from our hospital during December 2014 and December 2015 were enrolled in our study.The activity of RA was evaluated by the swollen joint count (SJC),tender joint count (TJC) and DAS28 score.The levels of serum Eotaxin-1 and antiCCP antibody were detected by ELISA and serum RF levels were determined by the immunological turbidimetry.The comparisons of serum Eotaxin-1,anti-CCP antibody and RF levels between different groups were performed with ANOVA and their correlations with SJC,TJC and DAS28 score were analyzed by Spearman rank correlation.Results The levels of Eotaxin-1,anti-CCP antibody and RF in RA patients were (96.02 ± 2 1.07) pg/mL,(183.42 ± 87.45) U/mL and (119.09 ± 62.30) RU/mL,respectively,which were significantly higher than those in the patients without RA and healthy controls (P ＜ 0.01).The levels of serum Eotaxin-1 in RA patients were significantly related to TJC,SJC and DAS28 score (P ＜ 0.01),while the levels of anti-CCP antibody were related to TJC and DAS28 score.The levels of RF were only related to DAS28 score.Conclusion The levels of serum Eotaxin-1 and anti-CCP antibody in RA patients are significantly correlated with the activity of RA,which may be new serum markers to monitor the activity of RA.

Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed 2 µg/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 µg/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ≥ 50 mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

Expression of Eotaxin and RANTES in Nasal Polyps versus Healthy Nasal Mucosa, a Case Control Study.

Aims: To investigate the levels of the chemokines; eotaxin and RANTES in chronic rhinosinusitsis with nasal polyposis in comparison to their levels in control healthy nasal mucosa to evaluate if they might play a role in pathogenesis. Study Design: We performed a prospective case control study. Place of Study and Duration: This study was performed in Otorhinolarngology Department Mansoura University Hospitals, Egypt. Methodology: It included 60 patients suffering from chronic rhinosinsuitis with nasal polyposis, in addition to 20 subjects that were included as control. Nasal tissue samples were collected from all cases and control to estimate the levels of eotaxin and RANTES by ELISA. Results: The estimated levels of eotaxin and RANTES in nasal polyps were higher than their measured levels in healthy nasal mucosa from control group and the results were statistically significant. Conclusion: The measured levels of eotaxin and RANTES suggest that they may have a role in pathogenesis of chronic rhinosinusitis with nasal polyposis and can be considered as a good target for medical therapy until supported by further studies.

Effect of ephedrine on expression of eotaxin in human bronchial epithelial cells stimulated by tumor necrosis factor-α / 重庆医学

Objective To observe the effect of ephedrine on the expression of eotaxin in human bronchial epithelial cells (16HBE) stimulated by tumor necrosis factor‐α(TNF‐α) and to explore the mechanism of Chinese medicine ephedra in treating asthma .Methods The in vitro cultured 16HBE were randomly divided into the control group ,TNF‐αstimulation group(TNF‐α20 ng/mL) and TNF‐αplus ephedrine group (TNF‐α20 ng/mL plus ephedrine 300 μg/mL) .Three complex holes in each group were set to culture for 18 h ,the eotaxin mRNA expression was measured by real time fluorescent quantified PCR and protein level was detected by immunocytochemical stain and Western blot .The eotaxin concentration in cells culture supernatant was quantified by ELISA .Results Compared with the the control group ,the expression level of eotaxin mRNA and protein ,and the concentration of eotaxin in cell culture supernatant in the TNF‐α stimulation group were increased obviously ,there being statisticaly significant difference between them(P<0 .01);however ,all above these parameters in the TNF‐αplus ephedrine group showed decreased obvi‐ously as compared with the TNF‐αgroup ,the difference between them was statistically significant (P<0 .01) .Conclusion Ephed‐rine can inhibit the expression and secretion of eotaxin in TNF‐α induced 16HBE inflammatory model ,which may be one of the mechanisms of Chinese medicine ephedra in treating asthma .

Effects of triptolide on airway remodeling as well as on STAT6 and eotaxin in asthmatic mice / 实用医学杂志

Objective To investigate the effect of triptolide on asthmatic airway remodeling and signal transducer and activator of transcription 6 (STAT6), acid neutrophil chemokines (eotaxin) impact. Methods The total of 30 mice with ovalbumin (OVA) model of asthma were randomly divided into three groups, control group, asthma group and triptolide group. After 24 hours of the last shot, lung tissue was stained Bronchial inflammatory cell infiltration was determined by using semi-quantitative method and calculate the proportion of goblet cells in airway epithelial cells. Hydroxyproline was determined by McMillan airway mucus score. The mRNA level and protein level of STAT6 and eotaxin in airway epithelium were determined by RT-PCR and immunohistochemistry. Results Compared with asthma group, peribronchial inflammatory cells infiltration of triptolide group were reduced, which mucus index is (1.31 ± 0.23) and hydroxyproline is (284 ± 13) μmg/100 mg. it had a significant in asthma group (P < 0.05). Besides, the protein level and mRNA level of STAT6 and eotaxin were significantly decreased (P < 0.05). Moreover, it was a positive correlation between STAT6 and eotaxin level in airway epithelial (r = 0.668, P < 0.05). Conclusion Triptolide can inhibit airway remodeling and might through the down regulation of STAT6 and eotaxin expression.

Research progress in chemokine receptor 3 and its ligands in ophthalmology / 中华实验眼科杂志

Chemokine receptor 3 (CCR3) and its ligands eotaxin are inflammatory factors,and they were thought to be related to asthma and allergic diseases before.Recent studies showed that CCR3 plays significant roles in many eye diseases,such as choroidal noevascularization (CNV),allergic cunjunctivititis,age-related macular degeneration (AMD),central retinal vein occlusion and retinal degeneration etc.The biological function study suggested that CCR3 and eotaxin participate in not only promoting the transportation of eosinophilic granulocyte and mastocyte but also inflammatory response.To understand the roles of CCR3 and eotaxin in eye diseases has a very important significance for the recognition and treatment of eye diseases.The structure and function of CCR3 and its ligands,and the relationship between CCR3 and some eye diseases were reviewed.

Expression and significance of eotaxin in nasal secretions / 重庆医学

Objective To discuss the expression and significance of eotaxin in the nasal secretions of the patients with nasal pol-yps .Methods The nasal secretion samples were collected from 40 patients including 15 cases of nasal polyps ,15 cases of chronic si-nusitis and 10 cases of nasal septum deviation .The enzyme-linked immunosorbent assay(ELISA) was adopted to detect the concen-tration of eotaxin .Results The average concentration of eotaxin was (468 .82 ± 440 .64)pg/mL in nasal polyps ,(443 .85 ± 334 .68) pg/mL in chronic sinusitis and (149 .23 ± 49 .01)pg/mL in nasal septum deviation .The eotaxin concentrations in the nasal polyps group and the chronic sinusitis group were higher than those in the nasal septum deviation group ,the difference was statistically significant(P<0 .05) .Conclusion The eotaxin concentration in the nasal secretions of the patients with nasal polyps is significantly increaseed ,which might be concluded that eotaxin may play an important role in the occurrence and development process of nasal polyps .

Gene-Gene Interaction Between CCR3 and Eotaxin Genes: The Relationship With Blood Eosinophilia in Asthma

PURPOSE: Eosinophils function as an effector cell in the development of asthma and allergic disease. Eotaxins are cytokines that promote pulmonary eosinophilia via the receptor CCR3. Single-nucleotide polymorphisms (SNPs) in CCR3 and eotaxin genes are associated with asthma. In this study, genetic interactions among SNPs of several eotaxin genes and CCR3 were assessed and their relationship with blood eosinophilia in asthma was examined. METHODS: A total of 533 asthmatics were enrolled in this study. Asthmatics with eosinophilia (>0.5x109/L) were compared with those without eosinophilia (A (29L>I) was significantly associated with 3 of the 4 CCR3 SNPs among asthmatics with eosinophilia (P=0.037-0.009). EOT2+304C>A (29L>I) and the CCR3 SNPs were also significantly associated with blood eosinophilia in an interaction model constructed by logistic regression (P=0.0087). GMDR analysis showed that the combination of EOT2+304C>A (29L>I) and CCR3-174C>T was the best model (accuracy=0.536, P=0.005, CVC 9/10). CONCLUSIONS: The epistatic influence of CCR3 on eotaxin gene variants indicates that these variants may be candidate markers for eosinophilia in asthma.

Oral Lovastatin Attenuates Airway Inflammation and Mucus Secretion in Ovalbumin-Induced Murine Model of Asthma

PURPOSE: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma. METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro. RESULTS: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells. CONCLUSIONS: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.

Eosinophil Development, Regulation of Eosinophil-Specific Genes, and Role of Eosinophils in the Pathogenesis of Asthma

Eosinophils arise from hematopoietic CD34+ stem cells in the bone marrow. They acquire IL-5Ralpha on their surface at a very early stage during eosinophilopoiesis, and differentiate under the strong influence of interleukin (IL)-5. They then exit to the bloodstream, and enter the lung upon exposure to airway inflammatory signals, including eotaxins. In inflamed tissues, eosinophils act as key mediators of terminal effector functions and innate immunity and in linking to adaptive immune responses. Transcription factors GATA-1, CCAAT/enhancer-binding protein, and PU.1 play instructive roles in eosinophil specification from multipotent stem cells through a network of cooperative and antagonistic interactions. Not surprisingly, the interplay of these transcription factors is instrumental in forming the regulatory circuit of expression of eosinophil-specific genes, encoding eosinophil major basic protein and neurotoxin, CC chemokine receptor 3 eotaxin receptor, and IL-5 receptor alpha. Interestingly, a common feature is that the critical cis-acting elements for these transcription factors are clustered in exon 1 and intron 1 of these genes rather than their promoters. Elucidation of the mechanism of eosinophil development and activation may lead to selective elimination of eosinophils in animals and human subjects. Furthermore, availability of a range of genetically modified mice lacking or overproducing eosinophil-specific genes will facilitate evaluation of the roles of eosinophils in the pathogenesis of asthma. This review summarizes eosinophil biology, focusing on development and regulation of eosinophil-specific genes, with a heavy emphasis on the causative link between eosinophils and pathological development of asthma using genetically modified mice as models of asthma.

The expression and clinical significance of the serum Eotaxin, IL-13 and total IgE in children with asthma / 国际儿科学杂志

Objective To study the nosogenesis and the relationship of different levels of serum Eotaxin,IL-13 and total IgE(TIgE)in asthmatic children. Methods Thirty children with asthma aging from 5 to 12 years were selected as study group (attack period and remission period), and 22 healthy children were selected as control group. Serum Eotaxin and IL-13 were measured with enzyme linked immunosorbent assay, and serum TIgE was determined with enzyme-linked fluoroimmune assay in the study group and control group, and pulmonary function was measured at the same time in the study group. Results (1) There were significant differences in pulmonary function between the attack period and the remission period (P ＜ 0. 001). (2) There were significant differences in the level of serum Eotaxin, IL-13 and IgE between the study group and the control group,especially for the attack period and the control group(P ＜0. 001). (3) There were significant positive correlations between the level of serum Eotaxin and IL-13, Eotaxin and TIgE, IL-13 and TIgE respectively in the study group (P ＜0. 05). (4) There were negative correlcations between the level of serum Eotaxin and FEV1 ,PEF,and serum IL-13 and FEV1, PEF in asthmatic children (P ＜ 0. 05), there were no correlations between the level of serum TIgE and FEV1, PEF in the study group (P ＞ 0. 05). Conclusion Serum Eotaxin, IL-13 and TIgE were participated in the nosogenesis of asthma, and the level of serum Eotaxin and IL-13 can be a assessment of asthmatic patients' condition.

Expression of eotaxin in 3T3-L1 adipocytes and the effects of weight loss in high-fat diet induced obese mice

Eotaxin is an important inflammatory chemokine in eosinophil chemotaxis and activation and, thus, is implicated in asthma. Recently, obesity was associated with an increased prevalence of asthma, but the relationship between obesity and eotaxin expression has only been partially understood in obese mice and human studies. Therefore, we studied the expression patterns of eotaxin in 3T3-L1 preadipocytes/adipocytes to determine whether eotaxin levels are influenced by body weight gain and/or reduction in diet-induced obese mice. First, we investigated eotaxin expression during differentiation in 3T3-L1 adipocytes. Then, we treated 3T3-L1 preadipocytes/adipocytes with tumor necrosis factor-alpha (TNF-alpha), eotaxin, interleukin (IL)-4, IL-5, or leptin. To examine the effects of weight loss in high-fat diet induced obese mice, we fed C57BL/6 mice a high-fat diet or a normal diet for 26 weeks. Then, half of the high-fat diet group were fed a normal diet until 30 weeks to reduce weight. Epididymal adipose tissue, visceral adipose tissue, serum, and bronchoalveolar fluid of mice were examined for eotaxin expression. The results showed that eotaxin expression levels increased with adipocyte differentiation and that more eotaxin was expressed when the cells were stimulated with TNF-alpha, eotaxin, IL-4, IL-5, or leptin. An in vivo study showed that eotaxin levels were reduced in visceral adipose tissues when high-fat diet fed mice underwent weight loss. Taken together, these results indicate a close relationship between eotaxin expression and obesity as well as weight loss, thus, they indirectly show a relation to asthma.

Genetic Association between Eotaxin Genes and Asthma and Its Relationship to Birth Season in Korean Children

Asthma is a chronic disease associated with airway constriction due to inflammation caused by eosinophils, mast cells, and T lymphocytes, leading to serious chronic illness in children. The eotaxin gene family has been shown to play an important role in the pathogenesis of asthma. We hypothesized that the distinctive variations among the four seasons in Korea may affect the expression of eotaxin polymorphisms, especially in children. We examined the possible effects of birth season (spring, March-May; summer, June-August; fall, September-November; and winter, December-February) on the phenotype of asthma in children. All SNP data sets of the eotaxin-2 and eotaxin-3 genes were collected from 78 asthma patients and 101 controls. Here, we investigated the effects of birth season on the expression of eotaxin-2 and eotaxin-3 in Korean children. Using the HAPLOTYPE procedure with the HTR method in SAS/Genetics, we showed that children born in spring and summer show significant haplotypes in both the eotaxin-2 and eotaxin-3 genes. Thus, the expression of polymorphisms in eotaxin-2 and eotaxin-3 may vary by season.

Association of single nucleotide polymorphisms in RANTES and Eotaxin-3 genes with childhood asthma / 上海交通大学学报（医学版）

Objective To investigate the association of single nucleotide polymorphisms(SNPs)in regulated upon activation normal T cell expressed and secreted (RANTES) gene C-28G(RANTES C-28G),RANTES A-403G and Eotaxin-3 gene C +77T(Eotaxin-3 C+77T) with asthma in Han ethnic children. Methods The buccal mucosa swabs of 192 Han ethnic children with asthma (asthma group) were collected,and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to detect the SNP loci of RANTES A-403G,C-28G and Eotaxin-3 C+77T.Besides,another 192 healthy subjects (aged 18 to 22 years) without sibship with those in asthma group were served as controls.Genotype and genotypic distribution between these two groups were analysed. Results There was no significant differences in genotype and genotypic distribution of SNP loci of RANTES A-403G and RANTES C-28G between asthma group and control group (P>0.05),while there were significant differences in genotypic distribution of Eotaxin-3 C+77T between these two groups.The frequency of Eotaxin-3 C+77T T/T genotype in asthma group was significantly higher than that in control group (32.3% vs 12.5%,OR=3.44,P=0.000). Conclusion Eotaxin-3 C+77T may be the asthma susceptible SNP loci for Han ethnic children,and Eotaxin-3 C+77T T/T is significantly related with the development of childhood asthma