Biomedical subjects

Shau-Ku Huang

Publications and source records attributed to Shau-Ku Huang.

26 records · Page 2Linked to original sources

PubMed2004

Current understanding and therapy of asthma workshop summary.

The prevalence of asthma has increased globally in the past 2 decades. To address this critical issue, a workshop on "Current Understanding and Therapy of Asthma" was recently held in Beijing, as a part of the 10th International Conference of the Society of Chinese Bioscientists in America (SCBA). Several pertinent topics were addressed by leading experts from China, Taiwan, Japan and the US, which include epidemiology, the molecular genetic mechanism, pathogenesis, treatment and prevention of asthma. This article highlights the issues presented and discussed in this ground-breaking symposium emphasizing this important public health problem in the Chinese population.

Anti-Inflammatory Agents↗

PubMed2003

Induction of C-X-C chemokines, growth-related oncogene alpha expression, and epithelial cell-derived neutrophil-activating protein-78 by ML-1 (interleukin-17F) involves activation of Raf1-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 pathway.

Neutrophil recruitment into the airway typifies pulmonary inflammation and is regulated through chemokine network, in which two C-X-C chemokines play a critical role. Airway epithelial cells and vein endothelial cells are major cell sources of chemokines. ML-1 (interleukin-17F) is a recently discovered cytokine and its function still remains elusive. In this report, we investigated the functional effect of ML-1 in the expression of growth-related oncogene (GRO)alpha and epithelial cell-derived neutrophil activating protein (ENA)-78. The results showed first that ML-1 induces, in time- and dose-dependent manners, the gene and protein expressions for both chemokines in normal human bronchial epithelial cells and human umbilical vein endothelial cells. Furthermore, selective mitogen-activated protein kinase kinase (MEK) inhibitors 2'-amino-3'-methoxyflavone (PD98059), 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126), and Raf1 kinase inhibitor I partially inhibited Ml-1-induced GROalpha and ENA-78 production. In contrast, the combination of PD98059 and Raf1 kinase inhibitor I completely abrogated the chemokine production, whereas a protein kinase C inhibitor, 2-(1-(3-aminopropyl) indol-3-yl)-3-(1-methylindol-3-yl) maleimide, acetate (Ro-31-7549), and a phosphatidylinositol 3-kinase inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), did not affect their production. Together, these data indicates a role for Raf1-MEK-extracellular signal-regulated kinase 1/2 pathway in ML-1 induced C-X-C chemokine expression, suggesting potential pharmacological targets for modulation.

Cells, Cultured↗

PubMed2003

Evidence for asthma susceptibility genes on chromosome 11 in an African-American population.

Initial genome-wide scan data provided suggestive evidence for linkage of the asthma phenotype in African-American (AA), but not Caucasian, families to chromosome 11q markers (peak at D11S1985; LOD=2). To refine this region, mapping analysis of 91 AA families (51 multiplex families and 40 asthmatic case-parent trios) was performed with an additional 17 markers flanking the initial peak linkage marker. Multipoint analyses of the 51 multiplex families yielded significant evidence of linkage with a peak non-parametric linkage score of 4.38 at marker D11S1337 (map position 68.6 cM). Furthermore, family-based association and transmission disequilibrium tests conducted on all 91 families showed significant evidence of linkage in the presence of disequilibrium for several individual markers in this region. A putative susceptibility locus was estimated to be at map position 70.8 cM with a confidence interval spanning the linkage peak. Evidence from both linkage and association analyses suggest that this region of chromosome 11 contains one or more susceptibility genes for asthma in these AA families.

Adolescent↗

PubMed2003

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study.

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.

Alleles↗

PubMed2002

Intranasal gene transfer by chitosan-DNA nanospheres protects BALB/c mice against acute respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is often associated in infancy with life-threatening bronchiolitis, which is also a major risk factor for the development of asthma. At present, no effective prophylaxis is available against RSV infection. Herein, we describe an effective prophylactic intranasal gene transfer strategy utilizing chitosan-DNA nanospheres (IGT), containing a cocktail of plasmid DNAs encoding all RSV antigens, except L. A single administration of IGT (25 microg/mouse) induces expression of the mRNA and proteins of all antigens in the lung and results in a significant reduction of viral titers and viral antigen load after acute RSV infection of these mice. IGT-administered mice show no significant change in airway reactivity to methacholine and no apparent pulmonary inflammation. Furthermore, IGT results in significant induction of RSV-specific IgG antibodies, nasal IgA antibodies, cytotoxic T lymphocytes, and interferon-gamma production in the lung and splenocytes compared with controls. Together, these results demonstrate the potential of IGT against acute RSV infection.

Animals↗

PubMed2002

Activation of extracellular signal-regulated kinase (ERK)1/2, but not p38 and c-Jun N-terminal kinase, is involved in signaling of a novel cytokine, ML-1.

A novel cytokine, ML-1, was recently discovered, which shares a similar sequence homology with, but is functionally distinct from, IL-17 (Kawaguchi, M., Onuchic, L., Li, X. D., Essayan, D. M., Schroeder, J., Xiao, H. Q., Liu, M. C., Krishnaswamy, G., Germino, G., and Huang, S. K. (2001) J. Immunol. 167, 4430-4435). To determine the signaling mechanisms of ML-1, we investigated activation of mitogen-activated protein (MAP) kinases induced by ML-1. Results show that ML-1 induces in a time-dependent fashion the expression of IL-6 and IL-8 in both primary bronchial epithelial cells (PBECs) and human umbilical vein endothelial cells (HUVECs). ML-1 activated a MAP kinase and an extracellular signal-regulated kinase (ERK)1/2 but not p38 or the c-Jun N-terminal kinase (JNK) in both cell types. Selective MAP kinase kinase (MEK)1/2 inhibitors, PD98059 and U0126, inhibited, in a dose-dependent manner, ML-1-induced expression of IL-6 and IL-8. These findings suggest that ML-1-induced IL-6 and IL-8 production is mediated through the activation of ERK1/2 in both cell types.

Animals↗

PubMed2002

Cell surface expression of a specific antigenic site on the catalytic subunit of (Na(+) + K(+))-ATPase.

Structural localization of a peptide region, KRQPRNPKTDKLVNE, in the catalytic subunit of (Na(+) + K(+))-ATPase was investigated using a specific antibody directed against this peptide in cultured African green monkey kidney CV-1 cells. Immunofluorescence staining of frozen cell sections shows that an anti-KRQPRNPKTDKLVNE antibody (SSA95) interacts with its antigenic site and binds to the extracellular side of the cell membrane. Indirect immunofluorescence and flow cytometric analyses confirmed the presence of this epitope on intact cell surfaces. These results suggest that the KRQPRNPKTDKLVNE region of the (Na(+) + K(+))-ATPase is expressed on the cellular membrane surface.

Amino Acid Sequence↗

PubMed2002

Regulation of eosinophil-active cytokine production from human cord blood-derived mast cells.

Human mast cells are multifunctional tissue-dwelling cells that play a crucial role in eosinophil-dependent disorders, such as asthma and parasitic diseases, by the secretion of eosinophil-active mediators. Mast cell-derived cytokines, generated in response to cross-linking of the high-affinity IgE receptor, can regulate eosinophil activation, survival, and chemotaxis. In this study, mast cells generated from human cord blood progenitors (stem cells) were studied for eosinophil-active inflammatory cytokine expression. Cord blood-derived mast cells (CBDMC) expressed typical intracellular scroll granules and microvilli-like structures on their cell surfaces, demonstrated the presence of tryptase, and elaborated prostaglandin D2 (PGD2) after cross-linkage of the high-affinity receptor for IgE (FcepsilonRI). CBDMC expressed tumor necrosis factor-alpha (TNF-alpha) and the eosinophil-active growth factors, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after activation. (IL-1beta greatly enhanced IgE-dependent production of these cytokines in response to FcepsilonRI cross-linkage, suggesting a role for bystander/phagocytic cells in modulating mast cell function. In contrast, interferon-alpha (IFN-alpha) inhibited IL-5 and GM-CSF generation, and the glucocorticoid, dexamethasone (Dex), inhibited production of IL-5 and GM-CSF from CBDMC. A macrophage-mast cell-eosinophil axis may exist in vivo that may be susceptible to pharmacologic manipulation.

Cells, Cultured↗