The synthesis of allergen‐specific IgE is required for the development of allergic diseases inclu... more The synthesis of allergen‐specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen‐specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen‐specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen‐specific IgE or IgG, epitope‐specificity of IgE and their degree of polyclonality (mono‐ vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FcɛRI) and other factors regulating the activation of FcɛRI‐bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are m...
Galectin-3 is an animal lectin, formerly named ε-binding protein or Mac-2, which has been describ... more Galectin-3 is an animal lectin, formerly named ε-binding protein or Mac-2, which has been described to play an important role in some inflammatory processes by the implication of different cells and the increase in cell adhesion functions through laminin binding activity. In this work we analyzed the role of galectin-3 in the modulation of Th2 cytokines that have an important role in the development of the inflammatory response. We have found that the addition of galectin-3 to human eosinophils, the eosinophilic cell line EoL-3, PBMC, and an Ag-specific T cell line (CD4+) produced a selective inhibition of IL-5 transcription. No inhibitory effect was found on the IL-4 mRNA transcription rate. The inhibitory effect on IL-5 transcription was reversed by incubation with lactose and using specific Ab against galectin-3. Galectin-3 is able to induce inhibition of the IL-5 released in the supernatants from PBMC stimulated with phorbol 12,13-dibutyrate and anti-CD3. Similar results were ob...
The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocesto... more The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocestoides corti was investigated by in situ hybridization technique. S35 labeled cDNA probe for alpha IL-1, hybridized with mRNA in murine eosinophils and macrophages. After 6 h of LPS stimulation eosinophils were able to express mRNA in their cytoplasm. This expression was highly increased by the addition of indomethacine. The IL-1 mRNA expression in murine macrophages was higher than in eosinophils in LPS-stimulated cells. This difference was statistically significant, p less than 0.001. To test if eosinophils may produce and release IL-1 in the culture medium, we isolated these cells in a Percoll gradient. Cell preparations with a purity exceeding 94% were cultured with various stimuli and their supernatants were tested for IL-1 activity. Eosinophils produced 169.65 +/- 73 U/ml when stimulated with LPS (n = 14). A dose-dependent response was obtained when the eosinophils were in the presen...
Journal of investigational allergology & clinical immunology, 2007
This study analyzes the influence of the IgE response to certain olive pollen allergens in the mo... more This study analyzes the influence of the IgE response to certain olive pollen allergens in the modulation of the different clinical phenotypes of allergic disease and their relationship with the level of exposure to pollen and genetic factors. Patients from high-exposure areas had a complex IgE antibody response to allergens of Olea euroapea, which included 3 or more allergens in 75% of cases. The majority allergens were Ole e 1, Ole e 2 (profilin), Ole e 7 (lipid transporting protein), Ole e 9 (glucanase), and Ole e 10. The existence of the antigen HLA-DR2 (15) led to a higher risk of sensitization to Ole e 10 and a greater trend towards the development of severe asthma, which increased in the presence of an anti-profilin IgE. Thirty percent of patients suffering from pollinosis simultaneously presented allergy to vegetable foods. Anti-Ole e 7 IgE was significantly associated with fruit anaphylaxis and anti-profilin IgE was detected in 90% of patients with oral syndrome. Finally, w...
Journal of investigational allergology & clinical immunology, 2007
This article summarizes the most important advances of recent years in the field of gene-environm... more This article summarizes the most important advances of recent years in the field of gene-environment interaction in allergic response. It specifically examines sensitization to olive pollen as an example of one of the main causes of allergic disease in the Mediterranean area. The presence of at least 20 proteins with allergic activity has been demonstrated in olive pollen, and 10 of these have been characterized (Ole e 1 to Ole e 10). Ole e 1, which is considered to be the majority allergen (causing sensitization in more than 70% of patients), has been the subject of many studies looking for risk factors and ways to protect against sensitization. Markers of the major histocompatibility complex and other genetic loci associated with the allergic response have been analyzed using population-based, family-based, and functional approaches, which have revealed the involvement of genetic regulation in this type of response. Furthermore, evaluation of environmental factors and their relati...
Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by... more Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2(PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/...
Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vul... more Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower tha...
This article contains information related to the research article entitled "Biomarkers assoc... more This article contains information related to the research article entitled "Biomarkers associated with disease severity in allergic and nonallergic asthma" (S. Baos, D. Calzada, L. Cremades, J. Sastre, J. Quiralte, F. Florido, C. Lahoz, B. Cárdaba, In press). Specifically, the clinical criteria stablished for selecting the study population (n=104 subjects) are described. Moreover, this article describes the criteria for selecting the 94 genes to be analyzed in PBMCs (peripheral blood mononuclear cells), it is provided a description of these genes and a Table with the genes most differentially expressed by clinical phenotypes and, finally it is detailed the experimental methodology followed for studying the protein expression of MSR1 (macrophage scavenger receptor 1), one of the genes evaluated in the research.
Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clin... more Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clinical pattern of asthma. This study analyzes the association between several polymorphims ofTNFA(G-308A,C-857T, andC-1031T),IL10(C-571AandA-1117G), andTGFB(C-509-T) and these sensitizations. These polymorphisms were genotyped by allelic discrimination, in olive pollen-allergic patients (phenotyped for specific Ole e 2 and 10 sensitizations) and healthy controls. Levels of serum-soluble cytokines were correlated with specific genotypes and clinical phenotypes. The results showed that heterozygousTGFB C-509Tgenotype, besides having the lowest sera TGF- levels, was significantly increased in olive pollen-allergic patients compared with controls. According specific sensitizations,CCgenotype ofIL10 C-571Acould be a protective factor for Ole e 2 sensitization and mainly for asthmatic Ole e 2 sensitized patients compared with asthmatic non-Ole e 2 sensitized patients (OR: 0.26,P=0.008). In contr...
Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic in... more Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 and Th2 cells. In a previous study, we demonstrated that treatment of chronic asthmatic mice with gene therapy using plasmid encoding galectin-3 (Gal-3) led to an improvement in Th2 allergic inflammation.Methods. Using a microarray approach, this study endeavored to evaluate the changes produced by therapeutic Gal-3 delivered by gene therapy in a well-characterized mouse model of chronic airway inflammation. Results were confirmed by real-time RT-PCR, Western blot and immunohistochemical analysis.Results. We identify a set of genes involved in different pathways whose expression is coordinately decreased/increased in mice treated with Gal-3 gene therapy. We report a c...
The synthesis of allergen‐specific IgE is required for the development of allergic diseases inclu... more The synthesis of allergen‐specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen‐specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen‐specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen‐specific IgE or IgG, epitope‐specificity of IgE and their degree of polyclonality (mono‐ vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FcɛRI) and other factors regulating the activation of FcɛRI‐bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are m...
Galectin-3 is an animal lectin, formerly named ε-binding protein or Mac-2, which has been describ... more Galectin-3 is an animal lectin, formerly named ε-binding protein or Mac-2, which has been described to play an important role in some inflammatory processes by the implication of different cells and the increase in cell adhesion functions through laminin binding activity. In this work we analyzed the role of galectin-3 in the modulation of Th2 cytokines that have an important role in the development of the inflammatory response. We have found that the addition of galectin-3 to human eosinophils, the eosinophilic cell line EoL-3, PBMC, and an Ag-specific T cell line (CD4+) produced a selective inhibition of IL-5 transcription. No inhibitory effect was found on the IL-4 mRNA transcription rate. The inhibitory effect on IL-5 transcription was reversed by incubation with lactose and using specific Ab against galectin-3. Galectin-3 is able to induce inhibition of the IL-5 released in the supernatants from PBMC stimulated with phorbol 12,13-dibutyrate and anti-CD3. Similar results were ob...
The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocesto... more The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocestoides corti was investigated by in situ hybridization technique. S35 labeled cDNA probe for alpha IL-1, hybridized with mRNA in murine eosinophils and macrophages. After 6 h of LPS stimulation eosinophils were able to express mRNA in their cytoplasm. This expression was highly increased by the addition of indomethacine. The IL-1 mRNA expression in murine macrophages was higher than in eosinophils in LPS-stimulated cells. This difference was statistically significant, p less than 0.001. To test if eosinophils may produce and release IL-1 in the culture medium, we isolated these cells in a Percoll gradient. Cell preparations with a purity exceeding 94% were cultured with various stimuli and their supernatants were tested for IL-1 activity. Eosinophils produced 169.65 +/- 73 U/ml when stimulated with LPS (n = 14). A dose-dependent response was obtained when the eosinophils were in the presen...
Journal of investigational allergology & clinical immunology, 2007
This study analyzes the influence of the IgE response to certain olive pollen allergens in the mo... more This study analyzes the influence of the IgE response to certain olive pollen allergens in the modulation of the different clinical phenotypes of allergic disease and their relationship with the level of exposure to pollen and genetic factors. Patients from high-exposure areas had a complex IgE antibody response to allergens of Olea euroapea, which included 3 or more allergens in 75% of cases. The majority allergens were Ole e 1, Ole e 2 (profilin), Ole e 7 (lipid transporting protein), Ole e 9 (glucanase), and Ole e 10. The existence of the antigen HLA-DR2 (15) led to a higher risk of sensitization to Ole e 10 and a greater trend towards the development of severe asthma, which increased in the presence of an anti-profilin IgE. Thirty percent of patients suffering from pollinosis simultaneously presented allergy to vegetable foods. Anti-Ole e 7 IgE was significantly associated with fruit anaphylaxis and anti-profilin IgE was detected in 90% of patients with oral syndrome. Finally, w...
Journal of investigational allergology & clinical immunology, 2007
This article summarizes the most important advances of recent years in the field of gene-environm... more This article summarizes the most important advances of recent years in the field of gene-environment interaction in allergic response. It specifically examines sensitization to olive pollen as an example of one of the main causes of allergic disease in the Mediterranean area. The presence of at least 20 proteins with allergic activity has been demonstrated in olive pollen, and 10 of these have been characterized (Ole e 1 to Ole e 10). Ole e 1, which is considered to be the majority allergen (causing sensitization in more than 70% of patients), has been the subject of many studies looking for risk factors and ways to protect against sensitization. Markers of the major histocompatibility complex and other genetic loci associated with the allergic response have been analyzed using population-based, family-based, and functional approaches, which have revealed the involvement of genetic regulation in this type of response. Furthermore, evaluation of environmental factors and their relati...
Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by... more Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2(PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/...
Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vul... more Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower tha...
This article contains information related to the research article entitled "Biomarkers assoc... more This article contains information related to the research article entitled "Biomarkers associated with disease severity in allergic and nonallergic asthma" (S. Baos, D. Calzada, L. Cremades, J. Sastre, J. Quiralte, F. Florido, C. Lahoz, B. Cárdaba, In press). Specifically, the clinical criteria stablished for selecting the study population (n=104 subjects) are described. Moreover, this article describes the criteria for selecting the 94 genes to be analyzed in PBMCs (peripheral blood mononuclear cells), it is provided a description of these genes and a Table with the genes most differentially expressed by clinical phenotypes and, finally it is detailed the experimental methodology followed for studying the protein expression of MSR1 (macrophage scavenger receptor 1), one of the genes evaluated in the research.
Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clin... more Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been correlated with a clinical pattern of asthma. This study analyzes the association between several polymorphims ofTNFA(G-308A,C-857T, andC-1031T),IL10(C-571AandA-1117G), andTGFB(C-509-T) and these sensitizations. These polymorphisms were genotyped by allelic discrimination, in olive pollen-allergic patients (phenotyped for specific Ole e 2 and 10 sensitizations) and healthy controls. Levels of serum-soluble cytokines were correlated with specific genotypes and clinical phenotypes. The results showed that heterozygousTGFB C-509Tgenotype, besides having the lowest sera TGF- levels, was significantly increased in olive pollen-allergic patients compared with controls. According specific sensitizations,CCgenotype ofIL10 C-571Acould be a protective factor for Ole e 2 sensitization and mainly for asthmatic Ole e 2 sensitized patients compared with asthmatic non-Ole e 2 sensitized patients (OR: 0.26,P=0.008). In contr...
Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic in... more Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 and Th2 cells. In a previous study, we demonstrated that treatment of chronic asthmatic mice with gene therapy using plasmid encoding galectin-3 (Gal-3) led to an improvement in Th2 allergic inflammation.Methods. Using a microarray approach, this study endeavored to evaluate the changes produced by therapeutic Gal-3 delivered by gene therapy in a well-characterized mouse model of chronic airway inflammation. Results were confirmed by real-time RT-PCR, Western blot and immunohistochemical analysis.Results. We identify a set of genes involved in different pathways whose expression is coordinately decreased/increased in mice treated with Gal-3 gene therapy. We report a c...
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