Loss of Interleukin-10 or Transforming Growth Factor β Signaling in the Human Colon Initiates a T-Helper 1 Response Via Distinct Pathways

1. Blood transfusion confers immune suppression with improved allograft survival. The aim of this study was to evaluate the effect of blood transfusion on the production of T-helper-2 cytokines and transforming growth factor β, which are associated with suppression of allograft rejection. An additional aim was to try to identify which blood cell type is mostly responsible for the blood transfusion effect. Production of interleukin-4, interleukin-10 and transforming growth factor β by peripheral blood mononuclear cells isolated from patients with end-stage renal disease was measured in vitro. These assays were performed before, and 4 h, 4, 7 and 14 days after a single blood transfusion and the transfusion of one unit of leucocyte-free erythrocytes. 2. Blood transfusion stimulated a significant rise in the production of all three cytokines measured. Transfusion of erythrocytes had no effect on the production of interleukin-4 or interleukin-10. 3. It is suggested that blood transfusion enhances the production of interleukin-4, interleukin-10 and transforming growth factor β. These cytokines may inhibit production of T-helper 1 and pro-inflammatory cytokines, deactivate cytotoxic cells and thereby suppress allograft rejection. It is further suggested that the leucocyte is the transfused cell type which is mostly associated with induction of this immunosuppressive response.

Download Full-text

Transforming growth factor β suppresses β-catenin/Wnt signaling and stimulates an adhesion response in human colon carcinoma cells in a Smad4/DPC4 independent manner

Cancer Letters ◽

10.1016/j.canlet.2008.01.039 ◽

2008 ◽

Vol 264 (2) ◽

pp. 281-287 ◽

Cited By ~ 12

Author(s):

Huijun Wang ◽

Shanthi Rajan ◽

Guangming Liu ◽

Subhas Chakrabarty

Keyword(s):

Growth Factor ◽

Wnt Signaling ◽

Colon Carcinoma ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Human Colon ◽

Carcinoma Cells ◽

Independent Manner ◽

Colon Carcinoma Cells ◽

Human Colon Carcinoma

Download Full-text

Mechanism of Transforming Growth Factor β–induced Inhibition of T Helper Type 1 Differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20012076 ◽

2002 ◽

Vol 195 (11) ◽

pp. 1499-1505 ◽

Cited By ~ 326

Author(s):

Leonid Gorelik ◽

Stephanie Constant ◽

Richard A. Flavell

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Inhibitory Effect ◽

Interleukin 12 ◽

T Helper ◽

Retroviral Transduction ◽

Cell Functions ◽

Proliferation And Differentiation ◽

Direct Inhibitory Effect

Regulation by transforming growth factor (TGF)-β plays an important role in immune homeostasis. TGF-β inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-β blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-β. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor β2 chain is not key to the TGF-β–mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-β on T cells is responsible, at least in part, for the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection.

Download Full-text

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

Infection and Immunity ◽

10.1128/iai.72.4.1974-1982.2004 ◽

2004 ◽

Vol 72 (4) ◽

pp. 1974-1982 ◽

Cited By ~ 52

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.

Download Full-text

Oral tolerance induced by continuous feeding: enhanced up-regulation of transforming growth factor-β/interleukin-10 and suppression of experimental autoimmune encephalomyelitis

Journal of Autoimmunity ◽

10.1016/s0896-8411(02)00112-9 ◽

2003 ◽

Vol 20 (2) ◽

pp. 135-145 ◽

Cited By ~ 91

Author(s):

Ana M.C. Faria ◽

Ruth Maron ◽

Sabine M. Ficker ◽

Anthony J. Slavin ◽

Thomas Spahn ◽

...

Keyword(s):

Growth Factor ◽

Experimental Autoimmune Encephalomyelitis ◽

Oral Tolerance ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Interleukin 10 ◽

Autoimmune Encephalomyelitis ◽

Continuous Feeding ◽

Experimental Autoimmune

Download Full-text

Phenotypic identification of CD19+CD5+CD1d+ regulatory B cells that produce interleukin 10 and transforming growth factor β 1 in human peripheral blood

Archives of Medical Science ◽

10.5114/aoms.2018.77772 ◽

2019 ◽

Vol 15 (5) ◽

pp. 1176-1183 ◽

Cited By ~ 2

Author(s):

Md Karim ◽

Yun-Fu Wang

Keyword(s):

B Cells ◽

Growth Factor ◽

Peripheral Blood ◽

Transforming Growth Factor ◽

Human Peripheral Blood ◽

Transforming Growth Factor Β ◽

Interleukin 10 ◽

Regulatory B Cells ◽

Phenotypic Identification

Download Full-text

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

Mediators of Inflammation ◽

10.1080/09629359891315 ◽

1998 ◽

Vol 7 (1) ◽

pp. 7-11 ◽

Cited By ~ 1

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.

Download Full-text