scholarly journals Down-Modulation of Lung Immune Responses by Interleukin-10 and Transforming Growth Factor β (TGF-β) and Analysis of TGF-β Receptors I and II in Active Tuberculosis

2004 ◽  
Vol 72 (5) ◽  
pp. 2628-2634 ◽  
Author(s):  
M. Glória Bonecini-Almeida ◽  
John L. Ho ◽  
Neio Boéchat ◽  
Richard C. Huard ◽  
Sadhana Chitale ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cellular Response ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Active Tuberculosis ◽  
Alveolar Cells ◽  
Old Patients ◽  
Protein Levels ◽  
Ifn Γ

ABSTRACT Immune factors influencing progression to active tuberculosis (TB) remain poorly defined. In this study, we investigated the expression of immunoregulatory cytokines and receptors by using lung bronchoalveolar lavage cells obtained from patients with pulmonary TB, patients with other lung diseases (OLD patients), and healthy volunteers (VOL) by using reverse transcriptase PCR, a transforming growth factor β (TGF-β) bioactivity assay, and an enzyme immunoassay. TB patients were significantly more likely than OLD patients to coexpress TGF-β receptor I (RI) and RII mRNA, as well as interleukin-10 (IL-10) mRNA (thereby indicating the state of active gene transcription in the alveolar cells at harvest). In contrast, gamma interferon (IFN-γ) and IL-2 mRNA was seen in both TB and OLD patients. Likewise, significantly elevated pulmonary steady-state protein levels of IL-10, IFN-γ, and bioactive TGF-β were found in TB patients versus those in OLD patients and VOL. These data suggest that the combined production of the immunosuppressants IL-10 and TGF-β, as well as coexpression of TGF-β RI and RII (required for cellular response to TGF-β), may act to down-modulate host anti-Mycobacterium tuberculosis immunity and thereby allow uncontrolled bacterial replication and overt disease. Delineating the underlying mechanisms of M. tuberculosis-triggered expression of these immune elements may provide a molecular-level understanding of TB immunopathogenesis.

scholarly journals Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival of Mycobacterium avium subsp. paratuberculosis in Monocyte-Derived Macrophages from Naturally Infected Cattle

2004 ◽  
Vol 72 (4) ◽  
pp. 1974-1982 ◽  
Author(s):  
M. S. Khalifeh ◽  
J. R. Stabel
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Mycobacterium Avium ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Culture Supernatants

ABSTRACT Gamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, including Mycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with live M. avium subsp. paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

Adipolin/CTRP12 protects against pathological vascular remodelling through suppression of smooth muscle cell growth and macrophage inflammatory response

2019 ◽  
Vol 116 (1) ◽  
pp. 237-249 ◽  
Author(s):  
Hayato Ogawa ◽  
Koji Ohashi ◽  
Masanori Ito ◽  
Rei Shibata ◽  
Noriyoshi Kanemura ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Transforming Growth Factor Β ◽  
Vascular Remodelling ◽  
Vsmc Proliferation ◽  
Protein Levels ◽  
Β Receptor

AbstractAimsSecreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodelling.Methods and resultsAdipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Adipolin deficiency also led to a reduction in transforming growth factor-β (TGF-β) 1 protein levels in injured arteries. Treatment of cultured macrophages with adipolin protein led to a reduction in lipopolysaccharide-stimulated expression of inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin (IL) 6, and monocyte chemotactic protein (MCP)-1. These effects were reversed by inhibition of TGF-β receptor II (TGF-βRII)/Smad2 signalling. Adipolin also reduced platelet-derived growth factor (PDGF)-BB-stimulated proliferation of vascular smooth muscle cells (VSMCs) through a TGF-βRII/Smad2-dependent pathway. Furthermore, adipolin treatment significantly increased TGF-β1 concentration in media from cultured VSMCs and macrophages.ConclusionThese data indicate that adipolin protects against the development of pathological vascular remodelling by attenuating macrophage inflammatory responses and VSMC proliferation.

scholarly journals The effect of interleukin-10 and transforming growth factor β-1 on HLA-DR expression in colonic epithelial cells

1998 ◽  
Vol 7 (1) ◽  
pp. 7-11 ◽  
Author(s):  
M. J. Zimmerman ◽  
G. R. Radford-Smith ◽  
D. P. Jewell
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Flow Cytometric Analysis ◽  
Biological Significance ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Colonic Epithelial Cells ◽  
Hla Dr ◽  
Dose Dependent Fashion

The aim of this study was to assess whether interleukin-10 (IL-10) and/or transforming growth factor β-1 (TGF β1) downregulate HLA-DR expression using the HT29 cell line as a model of colonic epithelial cells. HLA-DR expression was induced in HT29 cells withγ-interferon. The effects of IL-10 alone, TGF β1alone, and IL-10 and TGF β1in combination were studied. HLA-DR expression was assessed using flow cytometric analysis.γ-Interferon induced HLA-DR expression in a dose-dependent fashion. In the absence ofγ-interferon, neither IL-10 nor TGF β1induced HLA-DR expression. In isolation, neither IL10 nor TGF β1downregulated HLA-DR expression. When IL-10 and TGF β1were added in combination, small (6-30%) statistically significant reductions in HLA-DR expression were seen. The biological significance is unclear.

Interleukin-10 Regulates Transforming Growth Factor-β Signaling in Cultured Human Bronchial Epithelial Cells

Respiration ◽  
2007 ◽  
Vol 74 (4) ◽  
pp. 454-459 ◽  
Author(s):  
Naoto Fueki ◽  
Hironori Sagara ◽  
Kazumi Akimoto ◽  
Mayumi Ota ◽  
Takenori Okada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial

scholarly journals Chromatin-Bound p53 Anchors Activated Smads and the mSin3A Corepressor To Confer Transforming Growth Factor β-Mediated Transcription Repression

2008 ◽  
Vol 28 (6) ◽  
pp. 1988-1998 ◽  
Author(s):  
Deepti Srinivas Wilkinson ◽  
Wen-Wei Tsai ◽  
Maria A. Schumacher ◽  
Michelle Craig Barton
Keyword(s):  
Growth Factor ◽  
Tumor Marker ◽  
Transforming Growth Factor ◽  
Hepatoma Cell ◽  
Transforming Growth Factor Β ◽  
Regulatory Elements ◽  
Transcription Repression ◽  
Protein Levels ◽  
Smad Proteins ◽  
Distal Promoter

ABSTRACT In hepatic cells, Smad and SnoN proteins converge with p53 to repress transcription of AFP, an oncodevelopmental tumor marker aberrantly reactivated in hepatoma cells. Using p53- and SnoN-depleted hepatoma cell clones, we define a mechanism for repression mediated by this novel transcriptional partnership. We find that p53 anchors activated Smads and the corepressor mSin3A to the AFP distal promoter. Sequential chromatin immunoprecipitation analyses and molecular modeling indicate that p53 and Smad proteins simultaneously occupy overlapping p53 and Smad regulatory elements to establish repression of AFP transcription. In addition to its well-known function in antagonizing transforming growth factor β (TGF-β) responses, we find that SnoN actively participates in AFP repression by positively regulating mSin3A protein levels. We propose that activation of TGF-β signaling restores a dynamic interplay between p53 and TGF-β effectors that cooperate to effectively target mSin3A to tumor marker AFP and reestablish transcription repression.

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