scholarly journals Probiotic bacteriaBifidobacterium animalisMB5 andLactobacillus rhamnosusGG protect intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenicEscherichia coliK88

2006 ◽  
Vol 95 (6) ◽  
pp. 1177-1184 ◽  
Author(s):  
Marianna Roselli ◽  
Alberto Finamore ◽  
Maria Serena Britti ◽  
Elena Mengheri
Keyword(s):  
Transforming Growth Factor ◽  
Neutrophil Migration ◽  
Lactobacillus Rhamnosus ◽  
Intestinal Damage ◽  
Transforming Growth Factor Α ◽  
Bifidobacterium Animalis ◽  
Crucial Component ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α

Probiotic bacteria may provide protection against intestinal damage induced by pathogens, but the underlying mechanisms are still largely unknown. We investigated whetherBifidobacterium animalisMB5 andLactobacillus rhamnosusGG (LGG) protected intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenicEscherichia coli(ETEC) K88, by inhibiting pathogen attachment to the cells, which is the first step of ETEC pathogenicity, and regulating neutrophil recruitment, a crucial component of inflammation. A partial reduction of ETEC adhesion was exerted by probiotics and their culture supernatant fractions either undigested or digested with proteases. ETEC viability was unaffected by the presence ofB. animalis, LGG or their supernatant fractions in the culture medium, indicating an absence of probiotic bactericidal activity. Probiotics and their supernatant fractions, either undigested or digested with proteases, strongly inhibited the neutrophil transmigration caused by ETEC. BothB. animalisand LGG counteracted the pathogen-induced up regulation of IL-8, growth-related oncogene-α and epithelial neutrophil-activating peptide-78 gene expression, which are chemokines essential for neutrophil migration. Moreover, the probiotics prevented the ETEC-induced increased expression of IL-1β and TNF-α and decrease of transforming growth factor-α, which are regulators ofchemokine expression. These results indicate thatB. animalisMB5 and LGG protect intestinal cells from the inflammation-associated response caused by ETEC K88 by partly reducing pathogen adhesion and by counteracting neutrophil migration, probably through the regulation of chemokine and cytokine expression.

Recognition sequences and structural elements contribute to shedding susceptibility of membrane proteins

2001 ◽  
Vol 353 (3) ◽  
pp. 663-672 ◽  
Author(s):  
Katja ALTHOFF ◽  
Jürgen MÜLLBERG ◽  
Dorthe AASLAND ◽  
Nicole VOLTZ ◽  
Karl-Josef KALLEN ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Structural Changes ◽  
Phorbol Esters ◽  
Transforming Growth Factor ◽  
Proximal Region ◽  
Leukaemia Inhibitory Factor ◽  
Transforming Growth Factor Α ◽  
Tnf Α ◽  
Interleukin 6 Receptor ◽  
Factor Α

Although regulated ectodomain shedding affects a large panel of structurally and functionally unrelated proteins, little is known about the mechanisms controlling this process. Despite a lack of sequence similarities around cleavage sites, most proteins are shed in response to the stimulation of protein kinase C by phorbol esters. The signal-transducing receptor subunit gp130 is not a substrate of the regulated shedding machinery. We generated several chimaeric proteins of gp130 and the proteins tumour necrosis factor α (TNF-α), transforming growth factor α (TGF-α) and interleukin 6 receptor (IL-6R), which are known to be subject to shedding. By exchanging small peptide sequences of gp130 for cleavage-site peptides of TNF-α, TGF-α and IL-6R we showed that these short sequences conferred susceptibility to spontaneous and phorbol-ester-induced shedding of gp130. Importantly, these chimaeric gp130 proteins were functional, as shown by the phosphorylation of gp130 and the activation of signal transduction and activators of transcription 3 (‘STAT3’) on stimulation with cytokine. To investigate minimal requirements for shedding, truncated cleavage-site peptides of IL-6R were inserted into gp130. The resulting chimaeras were susceptible to shedding and showed the same cleavage pattern as observed in the chimaeras containing the complete IL-6R cleavage site. Surprisingly, we could also generate cleavable chimaeras by exchanging the juxtamembrane sequence of gp130 for the corresponding region of leukaemia inhibitory factor (‘LIF’) receptor, a protein that like gp130 is not subject to regulated or spontaneous shedding. Thus it seems that there is no minimal consensus shedding sequence. We speculate that structural changes allow the access of the protease to a membrane-proximal region, leading to shedding of the protein.

scholarly journals TNF-α Regulates Transforming Growth Factor-α Expression in Regenerating Murine Liver and Isolated Hepatocytes

2000 ◽  
Vol 164 (2) ◽  
pp. 872-878 ◽  
Author(s):  
Randle M. Gallucci ◽  
Petia P. Simeonova ◽  
Wataru Toriumi ◽  
Michael I. Luster
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Isolated Hepatocytes ◽  
Transforming Growth Factor Α ◽  
Tnf Α ◽  
Murine Liver ◽  
Factor Α

scholarly journals TGF-α increases human mesenchymal stem cell-secreted VEGF by MEK- and PI3-K- but not JNK- or ERK-dependent mechanisms

2008 ◽  
Vol 295 (4) ◽  
pp. R1115-R1123 ◽  
Author(s):  
Yue Wang ◽  
Paul R. Crisostomo ◽  
Meijing Wang ◽  
Troy A. Markel ◽  
Nathan M. Novotny ◽  
...  
Keyword(s):  
Low Dose ◽  
Kinase Inhibitors ◽  
Transforming Growth Factor ◽  
Human Mesenchymal Stem Cell ◽  
High Dose ◽  
Phosphatidylinositol 3 Kinase ◽  
Transforming Growth Factor Α ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells ◽  
Factor Α

Transforming growth factor-α (TGF-α) may be an important mediator of wound healing and the injury response. Human bone marrow mesenchymal stem cells (MSCs) release VEGF as a potentially beneficial paracrine response; however, it remains unknown whether TGF-α stimulates the production of VEGF from MSCs and, if so, by which mechanisms. We hypothesized that TGF-α would increase human MSC VEGF production by MAP kinase kinase (MAPKK/MEK), phosphatidylinositol 3-kinase (PI3-K)-, ERK, and JNK-dependent mechanisms. To study this, MSCs were cultured and divided into the following groups: 1) with vehicle; 2) with various stimulants alone: TGF-α, TNF-α, or TGF-α+TNF-α; 3) with individual kinase inhibitors alone (two different inhibitors for each of the following kinases: MEK, PI3-K, ERK, or JNK); and 4) with the above stimulants and each of the eight inhibitors. After 24-h incubation, a TGF-α dose-response curve demonstrated that low-dose TGF-α (500 pg/ml) suppressed MSC production of VEGF compared with vehicle (502 ± 16 pg/105cells/ml to 332 ± 9 pg/105cells/ml), while high-dose TGF-α (250 ng/ml) significantly increased MSC VEGF production (603 ± 24 pg/105cells/ml). High-dose TGF-α also increased TNF-α-stimulated release of VEGF from MSCs. MSCs exposed to TGF-α and/or TNF-α also demonstrated increased activation of PI3-K, JNK, and ERK. The TGF-α-stimulated production of VEGF by MSCs and the additive effect of TNF-α and TGF-α on VEGF production were abolished by MEK and PI3-K inhibition, but not ERK or JNK inhibition. Our data suggest that TGF-α increases VEGF production in MSCs via MEK- and PI3-K- but not ERK- or JNK-dependent mechanisms.

scholarly journals Tumor Necrosis Factor-α Triggers Mucus Production in Airway Epithelium through an IκB Kinase β-dependent Mechanism

2005 ◽  
Vol 280 (43) ◽  
pp. 36510-36517 ◽  
Author(s):  
José M. Lora ◽  
Dong Mei Zhang ◽  
Sha Mei Liao ◽  
Timothy Burwell ◽  
Anne Marie King ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Transforming Growth Factor ◽  
Mucus Production ◽  
Transforming Growth Factor Α ◽  
Iκb Kinase ◽  
Tnf Α ◽  
Factor Α

Excessive mucus production by airway epithelium is a major characteristic of a number of respiratory diseases, including asthma, chronic bronchitis, and cystic fibrosis. However, the signal transduction pathways leading to mucus production are poorly understood. Here we examined the potential role of IκB kinase β (IKKβ) in mucus synthesis in vitro and in vivo. Tumor necrosis factor-α (TNF-α) or transforming growth factor-α stimulation of human epithelial cells resulted in mucus secretion as measured by MUC5AC mRNA and protein. TNF-α stimulation induced IKKβ-dependent p65 nuclear translocation, mucus synthesis, and production of cytokines from epithelial cells. TNF-α, but not transforming growth factor-α, induced mucus production dependent on IKKβ-mediated NF-κB activation. In vivo, TNF-α induced NF-κB as determined by whole mouse body bioluminescence. This activation was localized to the epithelium as revealed by LacZ staining in NF-κB-LacZ transgenic mice. TNF-α-induced mucus production in vivo could also be inhibited by administration into the epithelium of an IKKβ dominant negative adenovirus. Taken together, our results demonstrated the important role of IKKβ in TNF-α-mediated mucus production in airway epithelium in vitro and in vivo.

Effects of transforming growth factor β, tumor necrosis factor α and interferon γ on pancreatic islet β-cell responsiveness to transforming growth factor α

1996 ◽  
Vol 16 (5) ◽  
pp. 415-423 ◽  
Author(s):  
Åke Sjöholm
Keyword(s):  
Insulin Secretion ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Insulin Content ◽  
Β Cell ◽  
Transforming Growth Factor Α ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α

The insulin-producing pancreatic islet β-cell, characterized by low proliferative potential, is normally not responsive to the polypeptide epidermal growth factor (EGF) or its homolog transforming growth factor α (TGF-α). Since EGF receptors in other tissues can be up-regulated by other growth factors and by cytokines, we have in this paper investigated whether such a β-cell responsiveness to TGF-α, or EGF, can be conferred by co-culture with interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) or transforming growth factor β (TGF-β) in various combinations. To this end, fetal rat pancreatic islets enriched in β-cells were isolated and cultured for 3 days with or without 200 pM or 20 nM TGF-α. It was found that neither of these TGF-α concentrations affected β-cell mitogenesis, insulin content or insulin secretion. However, IFN-γ (1000 U/ml) evoked a modest stimulation of β-cell replication, while suppressing insulin secretion and leaving the islet insulin content unaltered. TNF-α (1000 U/ml), on the other hand, affected none of these parameters either alone or in any combination with TGF-α or IFN-γ. However, when TNF-α or IFN-γ, either alone or in combination, were combined with the cytokine interleukin-1β, this resulted in islet disintegration, whereas the latter cytokine alone did not exert any gross necrotic changes evident by light microscopy. TGF-β (500 pM) stimulated insulin secretion but did not influence islet insulin content or β-cell mitogenesis either alone or in combination with TGF-α (200 pM or 20 nM). In no instance could any mitogenic or secretory response to low or high concentrations of TGF-α be conferred by IFN-γ, TNF-α or TGF-β whether used alone or in combinations. Hence, responsiveness to TGF-α or EGF in the β-cell obviously cannot be achieved by any of these peptides.

scholarly journals Metallothionein Expression and its Influence on the In Vitro Biological Behavior of Mucoepidermoid Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 157
Author(s):  
João Rafael Habib Souza Aquime ◽  
Lara Carolina D’Araújo Pinto Zampieri ◽  
Maria Sueli da Silva Kataoka ◽  
Nelson Antonio Bailão Ribeiro ◽  
Ruy Gastaldoni Jaeger ◽  
...  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Transforming Growth Factor Α ◽  
Protein Levels ◽  
Tnf Α ◽  
Factor Α

Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, often presenting with recurrence and metastasis due to its high invasive capacity. Metallothionein (MT), a zinc storage protein that supplies this element for protease activity, is probably related to mucoepidermoid carcinoma behavior. This prompted us to characterize a cell line derived from mucoepidermoid carcinoma and to correlate metallothionein expression with transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs). Transcriptomic analysis and cytogenetic assays were performed to detect the expression of genes of interest and cellular chromosomal alterations, respectively. MEC cells with a depleted metallothionein 2A (MT2A) gene were subjected to Western blot to correlate metallothionein expression with growth factors and MMPs. Additionally, cells with depleted MT were subjected to migration and invasion assays. The transcriptomic study revealed reads mapped to cytokeratins 19 and AE1/AE3, α-smooth muscle actin, vimentin, and fibronectin. Cytogenetic evaluation demonstrated structural and numerical alterations, including the translocation t(11;19)(q21;p13), characteristic of MEC. Metallothionein depletion was correlated with the decreased expression of TGF-α and MMP-9, while TNF-α protein levels were augmented. Migration and invasion activity were diminished after metallothionein silencing. Our findings suggest an important role of MT in MEC invasion, through the regulation of proteins involved in this process.

scholarly journals The Effects of Rice Husk Liquid Smoke in Porphyromonas gingivalis-Induced Periodontitis

2021 ◽  
Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah
Keyword(s):  
Growth Factor ◽  
Porphyromonas Gingivalis ◽  
Rice Husk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Proliferation Markers ◽  
Liquid Smoke ◽  
Tnf Α ◽  
Factor Α

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.

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