TGF-β: from latent to active

Khalil, Nasreen

doi:10.1016/s1286-4579(99)00259-2

Cited by 316 publications

(234 citation statements)

References 64 publications

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“…We have shown that SEA can induce Foxp3 expression in naïve CD4 1 T cells from NOD mice. We also found that SEA, in the absence of APC, can directly upregulate on NOD CD4 1 T cells expression of C-type lectin receptors (CLR) and surface-bound TGF-b, as determined by the presence of the latency-associated peptide (LAP) of TGF-b [5]. TGF-b is a central cytokine in the induction and maintenance of Treg but also in the induction of inflammatory Th17 cells [6].…”

Section: Introductionmentioning

confidence: 77%

Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

et al. 2010

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The immunomodulatory effect of Schistosoma mansoni antigens has often been attributed to interaction with PRR expressed on APC. Our previous work has shown that S. mansonisoluble egg antigen (SEA) can induce, together with a Th2 response, TGF-b-dependent Foxp3 expression in naïve CD4 1 T cells from NOD mice. We found that SEA can directly upregulate the expression of surface-bound TGF-b in purified CD4 1 T cells in the absence of accessory cell interactions. In this study, we show that the C-type lectin receptors DEC-205 and galectin-3 were involved in the direct interaction between S. mansoni antigens and CD4 1 T cells. SEA was able to enhance CD4 1 T-cell secretion of bioactive TGF-b in response to TLR2 ligand stimulation, in the absence of APC. We also show that TLR2 expressed on CD4 1 T cells was important for the Foxp3 expression induced by SEA.

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Section: Introductionmentioning

confidence: 77%

Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

et al. 2010

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“…Transforming growth factor-b is generally released from cells in a latent, biologically inactive form (Miyazono et al, 1993). Following release, it is activated by a variety of mechanisms, including exposure to proteolytic enzymes or alkaline pH conditions (Gleizes et al, 1997;Khalil, 1999). The presence of proteases in the pancreas and the alkaline pH of pancreatic juice may result in ideal conditions for activation of latent TGF-b.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

et al. 2004

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Pancreatic cancer is often associated with an intense production of interstitial collagens, known as the desmoplastic reaction. To understand more about desmoplasia in pancreatic cancer, the expression of mRNA for type I and III collagens and potent desmoplastic inducing growth factors transforming growth factor-b (TGF-b), connective tissue growth factor (CTGF), acidic and basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) A and C and epidermal growth factor (EGF) was analysed by quantitative RT-PCR. Expression of both collagens in 23 frozen primary pancreatic cancer nodules was significantly higher than that in 15 nonneoplastic pancreatic tissues. The expressions of mRNAs for TGF-b, acidic FGF, basic FGF and PDGF C were likewise higher in surgical cancer nodules, while that of CTGF, PDGF A and EGF were not. Among these growth factors, the expression of TGF-b mRNA showed the most significant correlation with that of collagens (Po0.0001). By immunohistochemistry, TGF-b showed faint cytoplasmic staining in cancer cells. In contrast, isolated cells, mainly located on the invasive front surrounding cancerous nests, were prominently and strongly stained. These TGF-b-positive cells contained a segmented nucleus, were negative for anti-macrophage (CD68) and positive for anti-granulocyte antibodies, indicating their granulocytic nature. In conclusion, TGF-b seemed to play a major role among the various growth factors in characteristic overproduction of collagens in pancreatic cancer. Moreover, the predominant cells that express TGF-b were likely to be infiltrated granulocytes (mostly are neutrophils) and not pancreatic cancer cells.

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“…TGFb is normally secreted in the latent form (L-TGFb), and must be cleaved from latency-associated peptides (LAP) to produce the bioactive form. 51 ROS are implicated in the activation of latent TGFb. 51 Quantification by staining with H2DCF-DA 42 established a higher prevalence of ROS in these cells ( Figure 4A, b).…”

Section: Activation Of Tgfb In Prdx6-depleted Lecs Is Associated Withmentioning

confidence: 99%

“…51 ROS are implicated in the activation of latent TGFb. 51 Quantification by staining with H2DCF-DA 42 established a higher prevalence of ROS in these cells ( Figure 4A, b). However, it is noteworthy that DCF fluorescence is not specific for H 2 O 2 , and other oxidants such as peroxynitrite, O 2 -, NO, etc.…”

Section: Activation Of Tgfb In Prdx6-depleted Lecs Is Associated Withmentioning

confidence: 99%

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

et al. 2005

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PRDX6, a member of the peroxiredoxins (PRDXs) family, is a key player in the removal of reactive oxygen species (ROS). Using targeted inactivation of the Prdx6 gene, we present evidence that the corresponding protein offsets the deleterious effects of ROS on lens epithelial cells (LECs) and regulates gene expression by limiting its levels. PRDX6-depleted LECs displayed phenotypic alterations and elevated a-smooth muscle actin and big-h3 expression (markers for cataractogenesis), indistinguishable from transforming growth factor b (TGFb)-induced changes. Biochemical assays disclosed enhanced levels of ROS, as well as high expression and activation of TGFb1 in Prdx6 À/À LECs. A CAT assay revealed transcriptional repression of lens epithelium-derived growth factor (LEDGF), HSP27, and aB-crystallin promoter activities in these cells. A gel mobility shift assay demonstrated the attenuation of LEDGF binding to heat shock or stress response elements present in these genes. A supply of PRDX6 toPrdx6 À/À LECs reversed these changes. Based on the above data, we propose a rheostat role for PRDX6 in regulating gene expression by controlling the ROS level to maintain cellular homeostasis.

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TGF-β: from latent to active

Cited by 316 publications

References 64 publications

Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

Overexpression of TGF-β by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

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