Interferon and Growth Factor Activity for Human Lung Fibroblasts

Moseley, Pope L.; Hemken, Chris; Monick, M. M.; Nugent, Kenneth; Hunninghake, Gary W.

doi:10.1378/chest.89.5.657

Cited by 45 publications

(7 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To evaluate the IL 2R in sarcoid, we have used a cDNA probe (pIL2R2) specific for the IL 2R p55-chain and a MAb (2A3) that is specific for the p55-chain protein (48), and have ensured that the IL 2R expressed by sarcoid T cells were functional by demonstrating that these cells respond to IL 2 by proliferating at a rate greater than that of normal cells. The finding that sarcoid lung T lymphocytes express IL 2R p55 surface protein and mRNA transcripts concurs with prior evidence of local activation of these cells at a site of disease (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)55 (30)(31)(32)(33). In comparison, the peak ofIL 2R mRNA transcripts, at least for the gene coding for the 55-kD IL 2R p55-chain, is later, with levels peaking at 24 h and mRNA transcripts easily detectable at 48 h. In sarcoid, evaluation of IL 2 mRNA transcripts in lung and blood of patients with active pulmonary sarcoidosis has shown that lung, but not blood, T cells contain these gene transcripts (21).…”

Section: Resultssupporting

confidence: 85%

“…In this context, evaluation of inflammatory cell populations in affected organs of individuals with active sarcoidosis has demonstrated increased numbers of CD4+ (helper/inducer) T cells that express surface activation markers such as the IL 2 receptor (IL 2R)' (10,11), D-related-antigen (8,11,12), 5/9 (13), and very late activation antigen-I (VLA-1) ( 14). Furthermore, these T cells at the site of disease proliferate at an exaggerated rate and release mediators typical of activated T lymphocytes,-including IL 2 (11,(15)(16)(17), IFN-y (18,19), monocyte chemotactic factor (4,13), and a nonspecific stimulus for Ig production by B lymphocytes (13,20). In comparison, evaluation of the blood ofthese individuals demonstrates decreased numbers and proportions ofCD4+ T cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.

Konishi¹,

Möller

Saltini

et al. 1988

J. Clin. Invest.

View full text Add to dashboard Cite

Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation in the local milieu. Normal clonal proliferation of T cells involves-activation and expression of the IL 2 receptor (IL 2R) gene. Thus, knowing that IL 2R mRNA transcripts are relatively long lived, we hypothesized that sarcoid blood T cells may contain IL 2R mRNA transcripts and express functional surface IL 2R, although the cells are probably activated elsewhere. Northern analysis using a 32P-labeled cDNA probe for the IL 2R p55 protein demonstrated that blood T cells of patients with active sarcoidosis, but not of normal patients, express 3.5-and 1.5-kb IL 2R mRNA transcripts, the same as those observed in normal T cells activated in vitro. Consistent with this, using flow cytometry and an MAb directed against the IL 2R p55 protein (2A3), we observed detectable levels of IL 2R surface protein on increased numbers of blood T cells of active sarcoidosis patients (4.7±0.9%) compared with blood.T cells of normal patients (0.9±0.2%). Importantly, when the sarcoid blood T cells were exposed to IL 2 in vitro, they proliferated at a rate greater than that of normal blood T cells under the same conditions, suggesting that the IL 2R spontaneously expressed by sarcoid blood T cells were functionally active. In the context of the known compartmentalization of spontaneous IL 2 production and T cell proliferation at sites of disease in active pulmonary sarcoidosis, these IL 2R positive blood T cells would probably have a proliferative advantage if they trafficked to sites of active sarcoidosis, such as the lower respiratory tract.

show abstract

Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.

Konishi¹,

Möller

Saltini

et al. 1988

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…IFNγ is a well established negative regulator of airway allergic immune responses [21]. The induction of IFNγ primarily is regulated by demethylation of CpG sites within the IFNγ gene [5,15,22].…”

Section: Introductionmentioning

confidence: 99%

Reproducibility and intraindividual variation over days in buccal cell DNA methylation of two asthma genes, interferon γ (IFNγ) and inducible nitric oxide synthase (iNOS)

et al. 2012

View full text Add to dashboard Cite

The biological mechanisms responsible for the onset and exacerbation of asthma symptoms in children may involve the epigenetic regulation of inflammatory genes after environmental exposures. Using buccal cells, we hypothesized that DNA methylation in promoter regions of two asthma genes, inducible nitric oxide synthase (iNOS) and interferon γ (IFNγ), can vary over several days. Repeat buccal samples were collected 4 to 7 days apart from 34 children participating in the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study. Several field duplicates (sequential collection of two samples in the field) and replicates (one sample pyrosequenced twice) also were collected to ensure consistency with collection and laboratory procedures. DNA methylation was assessed by pyrosequencing a PCR of bisulfite-treated DNA. We found that replicate and field duplicate samples were correlated strongly (r = 0.86 to 0.99, P < 0.05), while repeat samples demonstrated low within-subject correlations (r = 0.19 to 0.56, P = 0.06 to 0.30). Our data reveal DNA methylation as a dynamic epigenetic mechanism that can be accessed safely and reproducibly in an inner city pediatric cohort using non-invasive buccal swabs and pyrosequencing technology.

show abstract

“…The regulation of the immune response in pulmonary fibrosis has been studied in terms of the interaction between AM obtained from bronchoalveolar lavage (BAL) of diseased lungs and fibroblast cell lines obtained from normal lungs or organs with specific diseases [1,7,25,29]. Recent investigations have examined the function of fibroblasts derived from various diseases [19,24,28].…”

Section: Introductionmentioning

confidence: 99%

Fibroblasts as Target and Effector Cells in Japanese Patients with Sarcoidosis

Tamura

Sato

Chida

et al. 1998

Lung

View full text Add to dashboard Cite

Fibroblasts play a crucial role in progressive lung fibrosis, acting not only as target cells but also as effector cells. To clarify these functions in sarcoidosis, lung fibroblasts from Japanese sarcoid patients were studied for their proliferative capacity and cytokine productivity. Fibroblasts were cultured from transbronchial lung biopsy specimens from seven patients with sarcoidosis. As a comparison, fibroblasts from open lung biopsy specimens of four patients with idiopathic pulmonary fibrosis (IPF) were studied. For controls, fibroblasts were cultured from specimens of normal resected lung tissue of five patients with localized lung cancer. The proliferative activity of cultured fibroblasts from patients with sarcoidosis was highest among the three groups (p < 0.05). However, the proliferative capacity in all groups was suppressed when fibroblasts were cultured with interleukin-1beta (IL-1beta). No significant differences were noted in the degree of inhibition among the three groups. Addition of interferon-gamma (IFN-gamma) also resulted in inhibition of fibroblast growth in all groups, but the degree of inhibition was significantly greater in both the sarcoid and IPF groups than in controls (p < 0.05). The amount of interleukin-6 (IL-6) in the culture supernatants from sarcoid fibroblasts cocultured with IL-1beta was significantly higher than in controls. Sarcoid fibroblasts are not only proliferatively active but also possess effector cell function to produce cytokines. IL-6 may enhance the immunologic reaction to sarcoidosis and cause the disease to become chronic. IFN-gamma suppresses proliferation of sarcoid fibroblasts and may prevent fibrotic changes of the lungs in the Japanese sarcoid patients.

show abstract

Interferon and Growth Factor Activity for Human Lung Fibroblasts

Cited by 45 publications

References 17 publications

Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.

Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.

Reproducibility and intraindividual variation over days in buccal cell DNA methylation of two asthma genes, interferon γ (IFNγ) and inducible nitric oxide synthase (iNOS)

Fibroblasts as Target and Effector Cells in Japanese Patients with Sarcoidosis

Contact Info

Product

Resources

About