Serum-stimulated α1 type IV collagen gene transcription is mediated by TGF-β and inhibited by estradiol

1998 ◽  
Vol 274 (2) ◽  
pp. F252-F258 ◽  
Author(s):  
Jun Lei ◽  
Sharon Silbiger ◽  
Fuad N. Ziyadeh ◽  
Joel Neugarten
Keyword(s):  
Growth Factor ◽  
Gene Transcription ◽  
Type Iv Collagen ◽  
Transforming Growth Factor ◽  
Combined Treatment ◽  
Calf Serum ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Inhibitory Effect ◽  
Type Iv

We examined the hypothesis that fetal calf serum (FCS) stimulates murine mesangial cell α1 type IV collagen ( COL4A1) gene transcription by increasing autocrine production of transforming growth factor-β (TGF-β) through a platelet-derived growth factor (PDGF)-dependent mechanism. PDGF-stimulated COL4A1 gene transcription was inhibited by neutralizing antibody to TGF-β (119.3 ± 3.6 vs. 106.0 ± 6.2 relative luciferase units, expressed as a percentage of control untreated cells, P < 0.003). FCS-stimulated gene transcription was inhibited by neutralizing antibody to PDGF (148.3 ± 4.1 vs. 136.7 ± 0.3 relative luciferase units, P < 0.002) and by neutralizing antibody to TGF-β (148.3 ± 4.1 vs. 127.1 ± 3.4 relative luciferase units, P < 0.036). The inhibitory effect of combined treatment with anti-PDGF and anti-TGF-β antibody on gene transcription was no greater than that of anti-TGF-β antibody alone [129.5 ± 0.53 vs. 127.1 ± 3.4 relative luciferase units, P = not significant (NS)]. FCS-stimulated gene transcription was also inhibited by estradiol (10−7 M) (148.4 ± 3.1 vs. 119.4 ± 8.1 relative luciferase units, P < 0.019). In the presence of estradiol, anti-TGF-β antibody failed to further reduce serum-stimulated gene transcription (119.4 ± 8.1 vs. 115.6 ± 9.8, P = NS), suggesting that estradiol reverses FCS-stimulated COL4A1 gene transcription by antagonizing the actions of TGF-β. Measurement of type IV collagen synthesis by Western blotting confirmed that the intact gene responded in a manner analogous to the promoter construct.

scholarly journals Regulation of Interleukin-8 by Interleukin-10 and Transforming Growth Factor β in Human Monocytes Infected with Mycobacterium bovis

2002 ◽  
Vol 9 (4) ◽  
pp. 802-807 ◽  
Author(s):  
Patricia Méndez-Samperio ◽  
Elizabeth García ◽  
Abraham Vázquez ◽  
Janet Palma
Keyword(s):  
Growth Factor ◽  
Mycobacterium Bovis ◽  
Transforming Growth Factor ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Inhibitory Effect ◽  
Interleukin 8 ◽  
Mrna Levels ◽  
Human Monocytes

ABSTRACT Recent studies indicate that interleukin 8 (IL-8) production contributes to the host immune responses against mycobacterial infection. In this study, we were interested to determine whether induction of IL-8 in human monocytes infected with Mycobacterium bovis was regulated by other monocyte-derived cytokines important in antimycobacterial immunity: IL-10 and transforming growth factor β (TGF-β). Here, we report that IL-10 reduced, in a graded and significant manner, IL-8 production by M. bovis-infected human monocytes. Additionally, the specificity of the observed inhibition was further confirmed, since the addition of an anti-IL-10 neutralizing antibody completely reversed the inhibitory effect. In contrast, addition or neutralization of TGF-β appeared to have no significant effect on M. bovis-induced IL-8 secretion by human monocytes, whereas CD40 expression on M. bovis-infected monocytes was significantly inhibited by this cytokine. This was consistent with the finding by the reverse transcription-PCR method that pretreatment with IL-10, but not TGF-β, potently inhibited IL-8 mRNA levels. Interestingly, neutralization of endogenous IL-10 did not significantly alter IL-8 secretion, suggesting that induction of IL-8 was not significantly affected by coexpression of IL-10 during infection of human monocytes with M. bovis. Collectively, these data indicate that IL-8 production may be regulated when human monocytes are exposed to IL-10 prior to activation with M. bovis BCG. These data will aid in our understanding of the mechanisms involved in regulating the protective immune response to stimulation with M. bovis BCG.

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

2002 ◽  
Vol 195 (11) ◽  
pp. 1499-1505 ◽  
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.

Phenol red inhibits growth of renal epithelial cells

1992 ◽  
Vol 262 (4) ◽  
pp. F687-F691 ◽  
Author(s):  
M. M. Walsh-Reitz ◽  
F. G. Toback
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Calf Serum ◽  
Inhibitory Effect ◽  
Phenol Red ◽  
Mitogenic Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory

Phenol red coeluted with a novel kidney cell growth factor during its isolation from conditioned medium by high-performance liquid chromatography. The possibility that phenol red rather than the putative factor mediated the growth-promoting activity was tested, because this pH indicator is known to possess estrogenic properties including a mitogenic effect. Unexpectedly, phenol red at the concentration found in Dulbecco's modified Eagle's medium (DMEM) inhibited growth of monkey (BSC-1) and canine kidney (MDCK) epithelial cells by 20-30%, but stimulated multiplication of 3T3 fibroblasts. The growth-inhibitory effect of phenol red for BSC-1 cells was reversible, concentration dependent, and cell-density independent when multiplication was examined in the presence and absence of the dye. Phenol red partially masked the mitogenic effect of calf serum and epidermal growth factor and was additive to the growth-inhibitory effect of transforming growth factor-beta 2. These observations indicate that phenol red at the concentration in DMEM both underestimates the potency of mitogens and overestimates the strength of an inhibitor of kidney epithelial cell growth and suggest that the dye be omitted from the culture medium when a new growth-regulatory compound is under study.

Sign in / Sign up

Export Citation Format

Share Document