Biomedical subjects

Yong-Chul Lee

Publications and source records attributed to Yong-Chul Lee.

12 recordsLinked to original sources

PubMed2006

Gene-gene interaction between IL-13 and IL-13Ralpha1 is associated with total IgE in Korean children with atopic asthma.

Interleukin (IL)-13, which is essential for IgE synthesis, mediates its effects by binding with a receptor composed of IL-4Ralpha and IL-13Ralpha1. We investigated the effects of IL-13 and IL-13Ralpha1 polymorphisms in Korean children with asthma, and whether these have been associated with IgE production. We enrolled 358 atopic asthmatic, 111 non-atopic asthmatic, and 146 non-atopic healthy children. IL-13 and IL-13Ralpha1 genotypes were identified using the PCR-RFLP method. There was an association between the asthma susceptibility and homozygosity for risk allele of IL-13 G+2044A. In children with atopic asthma, risk alleles in IL-13 (A-1512C and C-1112T) and IL-13Ralpha1 (A+1398G) showed increased total IgE (P=0.012, 0.015 and 0.017, respectively). Three-loci haplotype analysis for IL-13 showed that the haplotype composed of -1512C, -1112T and +2044A was associated with higher total IgE than other tested haplotypes in children with atopic asthma (P=0.003). The gene-gene interaction between risk alleles of each IL-13 promoter polymorphism and IL-13Ralpha1 polymorphism was associated with higher total IgE in children with atopic asthma (P=0.002, 0.010). These findings indicate that the IL-13 G+2044A is associated with asthma development and the IL-13 and IL-13Ralpha1 polymorphisms may interact to enhance IgE production.

Asian People↗

PubMed2006

hKv1.5 channels play a pivotal role in the functions of human alveolar macrophages.

We examined the pharmacological properties, the molecular identity, and the functional roles of hKv1.5 channel in human alveolar macrophage. Some of outward K(+) current was inhibited by 4-aminopyridine and antisense oligodeoxynucleotides against hKv1.5 mRNA. Consistently, the protein and mRNA expressions of hKv1.5 channel were detected. Furthermore, the phagocytosis and migration of human alveolar macrophages were significantly suppressed when the protein expression of hKv1.5 channel was lowered by the antisense hKv1.5 oligodeoxynucleotides. These results suggest that hKv1.5 channel is expressed in human alveolar macrophages and it plays a role in phagocytosis and migration of the human alveolar macrophage.

4-Aminopyridine↗

PubMed2006

CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL-mediated osteoclastogenesis: evidence of NF-kappaB-dependent, CD40-mediated bone destruction in rheumatoid arthritis.

OBJECTIVE: To determine whether CD40 ligation of rheumatoid arthritis synovial fibroblasts (RASFs) is able to induce RANKL expression and osteoclastogenesis in RASFs, and to identify its mechanism of action in patients with RA. METHODS: CD40 of RASFs was ligated with CD40 ligand (CD40L)-transfected L cells or activated T cells. The formation of osteoclasts in cocultures of CD40-ligated RASFs and T lymphocyte-depleted peripheral blood mononuclear cells was evaluated by tartrate-resistant acid phosphatase staining, detection of calcitonin receptor, and resorption pit formation assay. The expression of NF-kappaB, IkappaB alpha, ERK-1/2, phospho-ERK-1/2, p38, phospho-p38, and RANKL was examined by immunoblotting and/or semiquantitative reverse transcription-polymerase chain reaction. RESULTS: CD40 ligation of RASFs by CD40L-transfected L cells or activated T cells induced RANKL expression and enhanced osteoclastogenesis. CD40 ligation of RASFs also induced activation of ERK-1/2, p38 MAPK, and NF-kappaB and up-regulation of CD40 ligation-induced RANKL expression, whereas osteoclastogenesis was reduced in RASFs transfected with a dominant-negative mutant of IkappaB alpha or by an NF-kappaB inhibitor. However, specific inhibitors of MAPK/ERK-1/2 and p38 MAPK partially blocked the induction of RANKL expression and osteoclastogenesis. Monoclonal antibodies against interleukin-1 and tumor necrosis factor alpha partially inhibited CD40 ligation-mediated osteoclastogenesis. CONCLUSION: These results indicate that CD40 ligation of RASFs induces RANKL expression mainly via NF-kappaB activation and also results in enhanced osteoclast formation, both of which might play important roles in bone and cartilage destruction in RA. Inhibition of the CD40-CD40L interaction is a potential strategy for the prevention of bone damage in RA.

Arthritis, Rheumatoid↗

PubMed2006

Plasma cell granuloma associated with pulmonary actinomycosis: a case report.

Plasma cell granuloma (PCG) of the lung is a rare disease that usually presents as a pulmonary nodule or mass on incidental radiographic examination without symptoms. Although the etiology of PCG is still controversial, many findings have lent support to the lesion being a reactive inflammatory process rather than a neoplastic one. We describe a 53-yr-old male who presented with a hemoptysis and have a lung mass at the left upper lobe on chest radiograph. The lung mass was primarily diagnosed as PCG by percutaneous needle aspiration and biopsy, and the patient was treated with oral steroid because he and relatives refused the operation. However, the size of the lung mass did not change and open thoracotomy and lobectomy were done therefore. He was confirmed as having pulmonary actinomycosis with PCG after surgery. To our knowledge, this is the first report of PCG associated with actinomycosis in Korea.

Actinomycosis↗

PubMed2005

TNF-alpha induces the late-phase airway hyperresponsiveness and airway inflammation through cytosolic phospholipase A(2) activation.

BACKGROUND: Late-phase airway hyperresponsiveness (AHR) in asthma is considered the event leading to persistent inflammation in the lungs, but the molecular mechanisms involved in this process are poorly understood. OBJECTIVE: To examine the role of TNF-alpha in the development of a late AHR and airway inflammation in asthma. METHODS: We established a murine model of asthma with not only biphasic AHR to methacholine but also airway eosinophilia. The effect of TNF-alpha blockade was determined by using anti-TNF-alpha antibody and TNF-alpha knockout mice. Cytosolic phospholipase A(2) (cPLA(2)) mRNA expression and activity were assessed by using RT-PCR and 1-stearoyl-2-[1-(14)C] arachidonyl-sn-glycero-3-phosphocholine as the substrate, respectively. RESULTS: TNF-alpha blockade resulted in significant inhibition of the late AHR without affecting the early AHR, and reduction in airway eosinophilia and inflammation. cPLA(2) activity was increased in asthmatic lungs in a TNF-alpha-dependent way, and cPLA(2) inhibitor blocked late AHR and airway eosinophilia. TNF-alpha also stimulated the synthesis of cPLA(2) metabolites such as leukotriene B(4) and platelet-activating factor in the airway. Specific inhibitors of cPLA(2) metabolites inhibited the late AHR and airway eosinophilia. CONCLUSIONS: TNF-alpha is the proximal key cytokine capable of developing late-phase AHR and subsequent airway inflammation through expression/activation of cPLA(2).

Animals↗

PubMed2005

Seroprevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in stable asthma and chronic obstructive pulmonary disease.

Mycoplasma pneumoniae and Chlamydia pneumoniae have been suggested to take part in the acute exacerbation of bronchial asthma and chronic obstructive pulmonary disease (COPD). Several studies have questioned whether they may play pathogenic roles in connection with bronchial asthma and COPD. This study was designed to evaluate the seroprevalences of M. pneumoniae and C. pneumoniae in stable asthma and COPD patients, and to compare with control patients. The medical records of one hundred forty patients who underwent M. pneumoniae and C. pneumoniae serology were retrospectively reviewed. Seroprevalences of M. pneumoniae and C. pneumoniae in the asthma group (11.1% and 8.3%, respectively) were higher than in the control group (4.4% and 2.2%, respectively) without statistical significance. The seroprevalence of M. pneumoniae in the COPD group (16.9%) was significantly higher than in the control group, and the seroprevalence of C. pneumoniae in the COPD group (3.4%) was higher than in the control group without statistical significance. This study raises important questions about the relation of M. pneumoniae and C. pneumoniae infection with stable asthma or COPD.

Adult↗

PubMed2004

The effect of long-term treatment with erythromycin on Th1 and Th2 cytokines in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a chronic progressive disease of the respiratory bronchioles, and has been improved by low-dose, long-term erythromycin (EMC) treatment. The therapeutic benefits may be derived from its anti-inflammatory and immunomodulatory properties rather than antimicrobial effect. However, there are few studies about the mechanism of immunomodulation by EMC treatment for patient with DPB. In this study, we quantified the changes of Th1 and Th2 cytokines in the bronchoalveolar lavage (BAL) fluid from patients with DPB after long term treatment with EMC. After the EMC treatment, a significant reduction in the number of lymphocytes was observed, and the CD4/CD8 ratio was elevated as well. The IL-2 and IFN-gamma levels in the BAL fluid were significantly decreased and the IL-4, IL-5, and IL-13 levels were significantly increased after EMC treatment. Our results suggest that the therapeutic benefits of long-term EMC treatment may be partially due to the immune system's shift from Th1 to Th2 cytokine production.

Adult↗

PubMed2004

Analysis of the polymorphisms in eotaxin gene family and their association with asthma, IgE, and eosinophil.

The eotaxin gene family (eotaxin, eotaxin-2, and eotaxin-3) has been implicated in the recruitment of eosinophils, basophiles, and Th2 lymphocytes that is a central aspect of allergic diseases such as asthma. To determine whether the single nucleotide polymorphisms (SNPs) of eotaxin gene family are associated with susceptibility to asthma, we scanned 225 asthma patients and 294 non-asthmatic controls using the direct sequencing method. We further investigated the relationships among each SNP, eosinophils, and serum total IgE levels in asthma patients. Eleven SNPs were identified in the eotaxin gene family. We found that EoB179T > C (P = 0.0001), EoB275C > T (P = 0.018) of the eotaxin-2 and EoA2497T > G (P = 0.003) of the eotaxin-3 were significantly associated with the susceptibility of asthma. Furthermore, our data demonstrated for the first time that EoA2497T > G (P = 0.005) is related to serum total IgE level while EoA77C > T (P = 0.035) and EoA2497T > G (P = 0.033) are related to the peripheral blood eosinophil counts in asthma. Our results suggest that the polymorphisms of the eotaxin gene family are associated with the susceptibility of asthma and Eotaxin-3 might play the critical role for the recruitment of eosinophils and the maintenance of IgE levels.

Adult↗

PubMed2004

Molecular variations in Th1-specific cell surface gene Tim-3.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.

Asthma↗

PubMed2004

The association of TIM-3 gene polymorphism with atopic disease in Korean population.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of the TIM family, TIM-3 is selectively expressed on the surface of differentiated T helper 1 (Th1) cells. TIM-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with the TIM-3 ligand to regulate Th1 responses. In the present study, we analyzed the association of the genotype and allele frequencies between asthma or allergic rhinitis patients and nonatopic controls using large samples size at -1516G > T, -574T > G, and 4259G > T polymorphic sites of the Tim-3 gene. The genotype and allele frequencies of -574T > G polymorphism in asthma patients (p = 0.042 and p = 0.017, respectively) as well as allergic rhinitis patients (p = 0.008 and p = 0.003, respectively) were significantly different from those of nonatopic controls. Furthermore, the allele frequency of 4259G > T polymorphism in allergic rhinitis patients (p = 0.029) was also significantly different. Our results strongly suggest that the -574T > G polymorphism of Tim-3 might be associated with the susceptibility of atopic diseases such as asthma and allergic rhinitis.

Adult↗

PubMed2003

The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and may be selectively expressed on Th2 cells. In the present study, we analyzed the association of allele and genotype frequencies between asthma or atopy patients and the controls without asthma and atopy using large sample size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene. Although the allele frequency of 5509_5511delCAA variation in asthma was not significantly different (P=0.085), the genotype of 5509_5511delCAA variation in asthma was significantly associated with the susceptibility to asthma (P=0.037). The genotype and allele frequencies of 5383_5397del variation in atopic dermatitis were significantly different from those in the non-asthmatic and non-atopic controls (P=0.005 and P=0.002, respectively). Our results strongly suggest that the 5383_5397del variation site of Tim-1 exon 4 might be associated with atopic dermatitis susceptibility.

Asthma↗

PubMed2003

Molecular variations in the promoter and coding regions of human Tim-1 gene and their association in Koreans with asthma.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, was considered as a membrane protein that is associated with the development of helper T cell (Th2) biased immune responses, and may be selectively expressed on Th2 cells. In the present study we performed single nucleotide polymorphism (SNP) scanning of the coding and promoter regions of human Tim-1 gene. We identified a total of ten SNPs including five novel SNPs (-1166C>G, -416G>C, -232A>G, 5365C>T, and 5529A>G) in the coding and promoter regions, one novel variation site (-2278_-2276dupATT) in the promoter region and three variations (5383_5397del, 5387_5389insAAC, and 5509_5511delCAA) in exon 4 of human Tim-1 gene. Our results suggest that the exon 4 variation site in human Tim-1 gene is associated with the susceptibility of allergic disease.

Asthma↗