BACKGROUNDInterleukin-4 (IL4) is one of the most important cytokines involved in a variety of allergic disorders, particularly, asthma. A number of genetic epidemiological studies have identified an association between the gene polymorphisms of IL4 and interleukin-4 receptor (IL4R) and asthma in different populations. However, these studies have been inconsistent and inconclusive. The aim of this study was to investigate the association between the single nucleotide polymorphism (SNP) of IL-4, IL-4R and asthma risk in case-controlled studies using meta-analysis.

METHODA genetic model-free approach was used to perform the meta-analysis. Asthma (atopy status nondefined), nonatopic and atopic asthma subgroups were separately analyzed. Next, the ethnic subgroup was analyzed. Heterogeneity and publication bias were also explored.

RESULTSOnly two polymorphisms of IL4 (rs2243250 and rs2070874) and four polymorphisms of IL4R (rs1801275, rs1805011, rs1805010, and rs1805015) were included in the meta-analysis. Polymorphisms rs2243250 and rs2070874 of IL-4 and rs1801275 and rs1805011 of IL4R were associated with asthma. The overall odds ratio (OR) of rs2243250 in the CC versus TT+TC genotypes was 0.84 (95% CI: 0.75-0.94), and the Z-test for the overall effect was 3.0 (P = 0.003). We obtained significant results from this polymorphism in the Caucasian ethnicity and adult groups. However, the overall OR of rs1801275 for the GG+AG versus AA genotype was 1.16 (95% CI: 1.00-1.35), and the Z-test for the overall effect was 1.87 (P = 0.06). Moreover, significant results were only obtained from the sub-group analysis in Asians (P = 0.02). In the rs1805011 polymorphism of IL4R, the overall OR for the CC +AC versus AA genotypes was 0.39 (95% CI: 0.16-0.95), and the Z-test for the overall effect was 2.08 (P = 0.04).

CONCLUSIONSBoth the IL4 and IL4R polymorphisms were associated with asthma. The rs2243250 polymorphism of IL4 was more important in the white and adult groups. Individuals who carried the C allele for rs2070874 of the IL4 gene demonstrated increased asthma risk compared to TT homozygotes. An individual with an AA genotype in rs1805011 of the IL4R gene was less likely to suffer from asthma compared to the other two genotypes.

Adult ; Asthma ; genetics ; Case-Control Studies ; Ethnic Groups ; Humans ; Interleukin-4 ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-4 ; genetics

The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) alpha chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in China was studied. By using case-control method, DNA and clinical data were obtained from allergic asthmatic patients and compared with those in the control subjects. The subjects were genotyped for the IL-4 C-589T promoter polymorphism, the IL-4R alpha chain Q576R and the AICDA C8408T by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results showed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, the IL-4R alpha chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthma group as compared with that in the control group [odd ratio (OR) = 3.797 and 9.127, respectively; P < 0.01)] and was correlated with the increased plasma total IgE. These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China.
Alleles ; Asthma/etiology ; Asthma/*genetics ; Cytidine Deaminase/*genetics ; Immunoglobulin E/blood ; Interleukin-4/*genetics ; Phenotype ; *Polymorphism, Restriction Fragment Length ; RNA Processing, Post-Transcriptional ; Receptors, Interleukin-4/*genetics

The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) alpha chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in China was studied. By using case-control method, DNA and clinical data were obtained from allergic asthmatic patients and compared with those in the control subjects. The subjects were genotyped for the IL-4 C-589T promoter polymorphism, the IL-4R alpha chain Q576R and the AICDA C8408T by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results showed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, the IL-4R alpha chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthma group as compared with that in the control group [odd ratio (OR) = 3.797 and 9.127, respectively; P < 0.01)] and was correlated with the increased plasma total IgE. These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China.
Adult ; Alleles ; Asthma ; etiology ; genetics ; Cytidine Deaminase ; genetics ; Humans ; Immunoglobulin E ; blood ; Interleukin-4 ; genetics ; Phenotype ; Polymorphism, Restriction Fragment Length ; RNA Processing, Post-Transcriptional ; Receptors, Interleukin-4 ; genetics

OBJECTIVETo assess the association of polymorphisms of IL-4 gene (rs2243250, rs2243283) and IL-4R gene (rs1805012, rs1801275, rs1805010) with susceptibility to asthma among ethnic Chinese in Qingdao.

METHODSFor 400 asthma patients and 200 healthy subjects, above polymorphisms were detected with SnaPshot method.

RESULTSFor rs1805012, the frequency of TC genotype in the asthma group was significantly lower than the control group (8.8% vs. 15.5%, χ (2)= 6.498, P= 0.039), and so were the frequencies of TC+ CC genotypes (9.0% vs. 15.5%, χ (2) = 5.522, P= 0.019) and the C allele (4.6% vs. 7.7%, χ (2) = 4.729, P= 0.039). No significant difference was detected between the two groups in the frequency of the remaining four polymorphisms or the haplotypes formed by rs2243250 and rs2243283 (All P> 0.05).

CONCLUSIONThis study has indicated that rs1805012 polymorphism of IL-4R gene is associated with asthma in ethnic Han Chinese from Qingdao region. TC+ CC genotypes have a protective role against asthma compared with TT genotype. However, polymorphisms of IL-4 gene are not associated with susceptibility to asthma.

Alleles ; Asian Continental Ancestry Group ; genetics ; Asthma ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-4 ; genetics ; Male ; Middle Aged ; Receptors, Interleukin-4 ; genetics

OBJECTIVETo investigate the expressions of chemokine receptors and interleukin (IL) receptors on the peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients and their correlations with clinical features as well as SLE disease activity index (SLEDAI).

METHODSThe mRNA expressions of chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy controls were detected by reverse transcription-polymerase chain reaction, including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCRS, CX3CR1, XCR1, IL-4R, and IL-10R. The clinical features of SLE patients were recorded. The correlations of chemokine receptors and IL receptors mRNA expressions with clinical features as well as SLEDAI were assayed using linear regression analysis.

RESULTSThe level of CCR5 mRNA in SLE patients (including active and inactive SLE) was significantly higher than that in healthy controls (P < 0.05), and there was no significant difference between active and inactive patients in this respect (P > 0.05). CX3CR1 mRNA expression significantly increased from healthy control to inactive SLE to active SLE in sequence. The others (except for CCR8, CXCR3, and IL-10R) in active SLE patients were significantly higher than those in both inactive SLE patients and healthy controls (all P < 0.05). There were positive correlations between SLEDAI and CCR2 (r = 0.424, t = 4.313, P < 0.001), CCR3 (r = 0.518, t = 5.410, P < 0.001), CCR4 (r = 0.376, t = 3.851, P < 0.001), CCR6 (r = 0.457, t = 4.513, P < 0.001), CXCR5 (r = 0.455, t = 4.629, P < 0.001), CX3CR1 (r = 0.445, t = 4.523, P < 0.001), as well as XCR1 (r = 0.540, t = 5.445, P < 0.001). And CCR5 mRNA expression level was positively correlated with IL-4R mRNA (r = 0.313, t = 2.353, P < 0.05). The patients with myositis and cutaneous vasculitis simultaneously showed lower levels of CCR5 and CX3CR1, and CCR5 expression was negatively correlated with the scores of SLEDAI in SLE cases accompanied by photosensitivity (r = 0.426, t = -2.155, P < 0.05).

CONCLUSIONIncreased expressions of CCR5 and CX3CR1 on PBMCs may be indicators in clinical survey for SLE.

Adolescent ; Adult ; CX3C Chemokine Receptor 1 ; Child ; Female ; Humans ; Leukocytes, Mononuclear ; immunology ; Lupus Erythematosus, Systemic ; etiology ; immunology ; Male ; Middle Aged ; RNA, Messenger ; blood ; Receptors, CCR5 ; genetics ; Receptors, Chemokine ; genetics ; Receptors, Interleukin-10 ; genetics ; Receptors, Interleukin-4 ; genetics

OBJECTIVETo study the correlations of IL-4R gene polymorphism and serum IgE levels with asthma predictive index (API) in children.

METHODSOne hundred and sixty-seven children with positive API, 187 children with negative API and 203 healthy children (control group) were enrolled. PCR and DNA sequencing were used to identify genotypes of the Arg551Gln locus in IL-4R gene. Serum IgE levels were measured using ELISA.

RESULTSThere was no significant difference in the genotype frequencies of the Arg551Gln locus in IL-4R gene among the positive API, negative API and control groups. Serum IgE levels in the positive API group were significantly higher than in the negative API and control groups (P<0.01). In the positive API group, the children aged less than 2 years had significantly lower serum IgE levels than those aged over 2 years (P<0.01).

CONCLUSIONSThere is no correlation between the Arg551Gln polymorphism in IL-4R gene and API results. API positivity is correlated with elevated serum IgE levels. An older age (>2 years) may be a risk factor for increased serum IgE levels in children with positive API.

Asthma ; blood ; genetics ; Child, Preschool ; Female ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Polymorphism, Genetic ; Receptors, Interleukin-4 ; genetics

OBJECTIVEInterleukin-4 plays a key role in the development of asthma. Overseas studies have shown that Q576R polymorphism in the interleukin-4 receptor (IL-4R) gene is related to asthma as well as increased serum IgE levels. This study was designed to investigate the association of Q576R polymorphism in IL-4R gene with childhood asthma and serum IgE levels.

METHODSThe polymorphism of IL-4R Q576R was determined by PCR/RFLP and serum total IgE level was measured using ELISA in 94 children with asthma. Sixty-eight healthy children served as controls.

RESULTSThe distribution frequency of heterozygous genotype Q576R (41%) and mutant allele R576 (26%) was significantly higher in children with asthma than that of controls (16% each) (P < 0.01; P < 0.05). The total serum IgE level between patients with genotype Q576R and Q576Q was not significantly different (225.78 +/- 51.43 IU/mL vs 163.24 +/- 31.32 IU/mL, P> 0.05).

CONCLUSIONSThe mutant R576 allele of IL-4R may be one of the candidate genes for susceptibility to asthma. Allele R576 of IL-4R is related to asthma but is irrelevant to the total serum IgE level in children with asthma.

Adolescent ; Asthma ; genetics ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Polymorphism, Genetic ; Receptors, Interleukin-4 ; genetics

BACKGROUNDCC chemokine receptor 3 (CCR3), expressed on some inflammatory cells, is a member of the chemokine receptor family. Its ligand is eotaxin/CCL11. In this research, we studied the expression and function of CCR3 induced by interleukin-2 (IL-2) and interleukin-4 (IL-4) on human germinal centre (GC) B cells.

METHODSCells isolated from human tonsils were stimulated with IL-2 or/and IL-4 followed by bonding with eotaxin/CCL11. Flow cytometry was used to detect expression of CCR3 on GC B cells and apoptosis of GC B cells. Real time quantitative reverse transcription polymerase chain reaction and Northern blot assays were used to analyse the CCR3 mRNA expressed in the GC B cells. Chemotaxis and adhesion assays were used to determine the effect of eotaxin/CCL11 ligand bonded to CCR3 on GC B cells.

RESULTSThere was no CCR3 expression on human freshly isolated GC B cells. The combination IL-2 and IL-4 could upregulate CCR3 mRNA and protein expression on GC B cells. Eotaxin could not induce GC B cell chemotaxis and adhesion but triggered apoptosis of GC B cells.

CONCLUSIONIL-2 and IL-4 together induced expression of CCR3 on GC B cells, and the receptor acted as a death receptor.

Apoptosis ; B-Lymphocytes ; metabolism ; pathology ; Cell Adhesion ; Chemotaxis, Leukocyte ; Germinal Center ; metabolism ; pathology ; Humans ; Interleukin-2 ; pharmacology ; Interleukin-4 ; pharmacology ; RNA, Messenger ; analysis ; Receptors, CCR3 ; Receptors, Chemokine ; genetics

Regulation of P2X7 receptor expression is of interest because activation of this receptor by extracellular ATP triggers a wide variety of cell functions in leukocytes. However, its expression and modulation in human peripheral blood mononuclear cells (PBMC) and monocytes remain unclear. RT-PCR was used to detect the constitutive level of P2X7 receptor and the levels upon stimulation with bacteria, bacterial product, mitogen and various cytokines in human PBMC and monocytes. P2X7 receptor mRNA was detected in PBMC and monocytes. P2X7 receptor expression in PBMC was up-regulated by interleukin-2, -4, -6 (IL-2, IL-4, IL-6) tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) and heat-inactivated Staphylococcus aureus Cowan strain I (SAC). However, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and phytohemagglutinin-M (PHA-M) had little effect on the expression of P2X7 receptor. Furthermore, LPS and M-CSF could up-regulate P2X7 receptor expression in monocytes, while IFN-gamma, TNF-alpha and GM-CSF had weak effects, but pretreatment with these inducers could not further enhance LPS-stimulated P2X7 receptor expression in monocytes. The results obtained demonstrate that inflammatory stimuli drive P2X7 expression, thus supporting the hypothesis that P2X7 receptor may play a role in the inflammatory responses against bacteria infection, which need further verification.
Humans ; Interleukin-2 ; physiology ; Interleukin-4 ; physiology ; Leukocytes, Mononuclear ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Receptors, Purinergic P2X7 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; physiology

OBJECTIVETo explore the effects of serum of asthmatic patients, dexamethasone, interleukin-4 (IL-4), interferon-gamma (IFN-γ) and transforming growth factor-β (TGF-β) on the expression of interleukin-22 receptor 1 (IL-22R1) mRNA and protein in HASMCs in vitro.

METHODSIL-22R1 mRNA and protein expressions in HASMCs treated with different stimulating agents were measured by real-time PCR and Western blotting, respectively.

RESULTSIL-22R1 mRNA and protein expressions in HASMCs were significantly increased after stimulation by serum from asthmatic patients, but decreased after co-stimulation with dexamethasone. IL-22R1 mRNA and protein expressions in the cells both increased after stimulation by IL-4, IFN-γ and TGF-β.

CONCLUSIONIL-22R1 in HASMCs might be involved in the pathogenesis of asthma, and the therapeutic effect of dexamethasone on asthma is mediated, at least partially, by IL-22R1. The effects of IFN-γ, IL-4, and TGF-β on asthma may also be attributed to their actions on HASMCs.

Asthma ; blood ; Cell Line ; Humans ; Interferon-gamma ; pharmacology ; Interleukin-4 ; pharmacology ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Receptors, Interleukin ; metabolism ; Transforming Growth Factor beta ; pharmacology