Analysis of Cytokine Transcripts in the Bronchoalveolar Lavage Cells of Patients with Asthma

Krishnaswamy, Guha; Liu, Mark C.; Su, Song‐Nan; Kumai, Megumi; Xiao, Huamei; Marsh, David G.; Huang, Shau‐Ku

doi:10.1165/ajrcmb/9.3.279

Cited by 84 publications

(35 citation statements)

References 19 publications

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“…The intensity of IL-5 mRNAexpression correlated well with that of eosinophilic infiltration, whereas that of IL-3 and GM-CSF did not (12). Wehave reported that IL-5 production by CD4+T cells of asthmatic patients is significantly enhanced compared to that of healthy controls (13).…”

Section: Introductionmentioning

confidence: 65%

Transcriptional Regulation of IL-5 Gene by Nontransformed Human T Cells Through the Proximal Promoter Element.

et al. 2000

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Objective IL-5 is strongly involved in the eosinophilic inflammation in bronchial asthma and atopic dermatitis. Wehave previously reported that IL-5 synthesis in atopic and nonatopic asthmatics is significantly enhanced compared to control subjects. T cell IL-5 synthesis is regulated through several transcriptional elements, one of which is the proximal human IL-5 promoter (-62 to -46). The present study was undertaken to delineate the transcriptional regulation through this element using nontransformed human T cells. Methods Con A blast lymphocytes which tolerate electroporation were derived from peripheral blood lymphocytes. Luciferase reporter analysis and gel shift analysis were performed. Results The proximal promoter element is the overlapping binding site for the constitutive binding factor, Oct-1, and the inducible one, AP-1. The transcriptional induction was ascribed to the inducible binding, while the constitutive binding was rather inhibitory. A mutant element which lost the constitutive binding but retained the inducible binding exerted 3 times more transcriptional activity compared to the wild type element. In contrast, another mutant element which lost the inducible binding and retained the constitutive binding exhibited no transcriptional induction. Gel shift analysis clarified that the inducible binding was more prominent and the constitutive binding was less in IL-5-producing T cells derived from asthma patients compared to IL-5-nonproducing cells derived from control subjects. Conclusions The ratio of the inducible/constitutive binding to the proximal promoter element maydetermine the capacity of human Th cells to transcribe IL-5 gene, and its regulation may control eosinophilic inflammation. (Internal Medicine 39: 618-625, 2000)

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Section: Introductionmentioning

confidence: 65%

Transcriptional Regulation of IL-5 Gene by Nontransformed Human T Cells Through the Proximal Promoter Element.

et al. 2000

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“…Increasing evidence places IL-5 in a key role in the development of eosinophilia in asthma (5,6). IL-5 mRNA was significantly enhanced in bronchoalveolar lavage cells obtained from asthmatics challenged with ragweed antigen (8). Again, peripheral blood T cells from asthmatics were found to secrete IL-5 in response to the common house dust mite (Dermatophagoides farinae) antigen (13).…”

mentioning

confidence: 96%

“…good evidence that in atopic asthmatics, a Th2-type response occurs in the airways (5)(6)(7)(8). Although it appears that the outcome of many diseases such as asthma is determined by the ratio of Th1 to Th2 cells (4), the molecular basis for Th1-and Th2-specific gene expression remains to be elucidated.…”

mentioning

confidence: 99%

Transcription Factor GATA-3 Is Differentially Expressed in Murine Th1 and Th2 Cells and Controls Th2-specific Expression of the Interleukin-5 Gene

Zhang¹,

Cohn²,

Ray³

et al. 1997

Journal of Biological Chemistry

596

486

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Interleukin-5 (IL-5), which is produced by CD4؉ T helper 2 (Th2) cells, but not by Th1 cells, plays a key role in the development of eosinophilia in asthma. Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of CD4 ؉ T helper cells, Th1 and Th2, the molecular basis for Th1-and Th2-specific gene expression remains to be elucidated. We previously established a critical role for the transcription factor GATA-3 in IL-5 promoter activation in EL-4 cells, which express both Th1-and Th2-type cytokines. Our studies reported here demonstrate that GATA-3 is critical for expression of the IL-5 gene in bona fide

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“…The lung inflammatory responses in asthma are tightly associated with airway hyperresponsiveness, and Th2 cells play a critical role in initiating and sustaining asthmatic lung inflammation. In asthma patients, activated CD4 ϩ T cells with predominant Th2 type cytokine (IL-4 and IL-5) expression are present in bronchoalveolar lavage (BAL) fluid and in lung biopsies (2)(3)(4)(5). In murine models, the importance of CD4 ϩ Th2 cells in the development of pulmonary allergic inflammation has also been demonstrated.…”

mentioning

confidence: 99%

Allergen-Induced Airway Hyperreactivity Is Diminished in CD81-Deficient Mice

Deng¹,

Yeung

Tsitoura

et al. 2000

The Journal of Immunology

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We demonstrated previously that CD81−/− mice have an impaired Th2 response. To determine whether this impairment affected allergen-induced airway hyperreactivity (AHR), CD81−/− BALB/c mice and CD81+/+ littermates were sensitized i.p. and challenged intranasally with OVA. Although wild type developed severe AHR, CD81−/− mice showed normal airway reactivity and reduced airway inflammation. Nevertheless, OVA-specific T cell proliferation was similar in both groups of mice. Analysis of cytokines secreted by the responding CD81−/− T cells, particularly those derived from peribronchial draining lymph nodes, revealed a dramatic reduction in IL-4, IL-5, and IL-13 synthesis. The decrease in cytokine production was not due to an intrinsic T cell deficiency because naive CD81−/− T cells responded to polyclonal Th1 and Th2 stimulation with normal proliferation and cytokine production. Moreover, there was an increase in T cells and a decrease in B cells in peribronchial lymph nodes and in spleens of immunized CD81−/− mice compared with wild-type animals. Interestingly, OVA-specific Ig levels, including IgE, were similar in CD81−/− and CD81+/+ mice. Thus, CD81 plays a role in the development of AHR not by influencing Ag-specific IgE production but by regulating local cytokine production.

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Analysis of Cytokine Transcripts in the Bronchoalveolar Lavage Cells of Patients with Asthma

Cited by 84 publications

References 19 publications

Transcriptional Regulation of IL-5 Gene by Nontransformed Human T Cells Through the Proximal Promoter Element.

Transcriptional Regulation of IL-5 Gene by Nontransformed Human T Cells Through the Proximal Promoter Element.

Transcription Factor GATA-3 Is Differentially Expressed in Murine Th1 and Th2 Cells and Controls Th2-specific Expression of the Interleukin-5 Gene

Allergen-Induced Airway Hyperreactivity Is Diminished in CD81-Deficient Mice

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