Trefoil factor 3 shows anti-inflammatory effects on activated microglia

Arnold, Philipp; Rickert, U.G.; Helmers, Ann‐Kristin; Spreu, Jessica; Schneppenheim, Janna; Lucius, Ralph

doi:10.1007/s00441-016-2370-5

Cited by 19 publications

(22 citation statements)

References 39 publications

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“…Isolation of primary microglia always involves the risk of co-purification of other cells from the CNS specifically astrocytes are prone to co-purification and maintenance. To exclude contamination, we performed immunocytochemistry and stained for the microglia marker CD11b (Integrin αM) using the OX-42 antibody as reported before [17] ( Fig. 1 A).…”

Section: Resultsmentioning

confidence: 99%

“…Cells were seeded on glass cover slips and allowed to adhere overnight. Cells were fixed (4% Paraformaldehyde and 0.2% picric acid in PBS) and antibodies against GFAP (1:500) (Santa Cruz Biotechnology) and OX42 (1:200) (AbCam) were used as described [17] . Translocation of NFκB was assessed as described before [ 17 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…Cells were fixed (4% Paraformaldehyde and 0.2% picric acid in PBS) and antibodies against GFAP (1:500) (Santa Cruz Biotechnology) and OX42 (1:200) (AbCam) were used as described [17] . Translocation of NFκB was assessed as described before [ 17 , 18 ]. Briefly, cells were seeded on glass slides, stimulated with PBS (control), 200 mM Aldosterone, 5 ng/ml LPS or 200 nM Aldosterone and 5 ng/ml LPS for 60 min and fixed afterwards (4% paraformaldehyde and 0.2% picric acid in PBS).…”

Section: Methodsmentioning

confidence: 99%

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Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia

Bast

Rickert

Schneppenheim

et al. 2018

Heliyon

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Over the last years, studies on microglia cell function in chronic neuro-inflammation and neuronal necrosis pointed towards an eminent role of these cells in Multiple Sclerosis, Parkinson's and Alzheimer's Disease. It was found, that microglia cell activity can be stimulated towards a pro- or an anti-inflammatory profile, depending on the stimulating signals. Therefore, investigation of receptors expressed by microglia cells and ligands influencing their activation state is of eminent interest.A receptor found to be expressed by microglia cells is the mineralocorticoid receptor. One of its ligands is Aldosterone, a naturally produced steroid hormone of the adrenal cortex, which mainly induces homeostatic and renal effects. We evaluated if the addition of Aldosterone to LPS stimulated microglia cells changes their inflammatory profile.Therefore, we assessed the levels of nitric oxide (NO), iNOS, IL-6, IL-1β, TNF-α and COX-2 in untreated, LPS-treated and LPS/Aldosterone-treated microglia cells. Furthermore we analyzed p38-MAP-Kinase and NFκB signaling within these cells.Our results indicate that the co-stimulation with Aldosterone leads to a decrease of the LPS-induced pro-inflammatory effect and thus renders Aldosterone an anti-inflammatory agent in our model system.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia

Bast

Rickert

Schneppenheim

et al. 2018

Heliyon

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“…Samples were embedded in paraffin and sectioned into 7 µm slices. H&E staining was performed following routine protocols (Arnold et al, 2016).…”

Section: Histology and Immunofluorescencementioning

confidence: 99%

The cancer-associated meprin β variant G32R provides an additional activation site and promotes cancer cell invasion

Schäffler¹,

Li²,

Helm³

et al. 2019

Journal of Cell Science

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The extracellular metalloprotease meprin β is expressed as a homodimer and is primarily membrane bound. Meprin β can be released from the cell surface by its known sheddases ADAM10 and ADAM17. Activation of pro-meprin β at the cell surface prevents its shedding, thereby stabilizing its proteolytic activity at the plasma membrane. We show that a single amino acid exchange variant (G32R) of meprin β, identified in endometrium cancer, is more active against a peptide substrate and the IL-6 receptor than wild-type meprin β. We demonstrate that the change to an arginine residue at position 32 represents an additional activation site used by furin-like proteases in the Golgi, which consequently leads to reduced shedding by ADAM17. We investigated this meprin β G32R variant to assess cell proliferation, invasion through a collagen IV matrix and outgrowth from tumor spheroids. We found that increased meprin β G32R activity at the cell surface reduces cell proliferation, but increases cell invasion.

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“…The interaction between TFF3 and mucins has also been reported to protect intestinal epithelia from injuries, maintaining mucosal barrier function (26). Furthermore, mitogenic effects of TFF3 have been identified in vitro in primary cell culture, and TFF3 has been demonstrated to inhibit apoptosis, induce cellular invasion, act as an inflammatory modulator and exhibit pro-angiogenic activity (27)(28)(29)(30)(31)(32). A protective or healing effect of TFF3 has also been reported in a series of experiments, such as cells in vitro, mice, rats and human (12)(13)(14)(15)(16)(17).…”

Section: Discussionmentioning

confidence: 99%

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

Wen

et al. 2020

Exp Ther Med

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Trefoil factor 3 (TFF3) is involved in cell adhesion, motility and apoptosis, regulates mucosal immunity and maintains the functional integrity of intestinal epithelia. The upregulation of TFF3 expression in the weaning rat intestine attracted our interest. The present study hypothesized that TFF3 may serve a role in preventing diarrhea in weaning piglets, which is an important consideration in the pig farming industry. Previous recombinant TFF3 protein expression yields obtained from Escherichia coli were too low and the bioactivity of the protein was poor. Hence, this expression system was unsuitable for industrial applications. The present study explored the production of recombinant sus scrofa TFF3 in a Brevibacillus choshinensis (B. choshinensis) expression system, aiming to enhance the expression level of bioactive protein. To achieve this, the sus scrofa TFF3-encoding gene fragment was fused into an E. coli-Brevibacillus shuttle vector pNCMO2. High levels of TFF3 (30 mg/l) were produced and secreted into the B. choshinensis culture medium in soluble form with a molecular mass of 13.6 kDa and high immunoreactivity in western blotting. Thus, Brevibacillus may be used to produce useful mucosal factors for biochemical analyses and mucosal protection, and in industrial applications to produce novel inhibitors of diarrhea.

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Trefoil factor 3 shows anti-inflammatory effects on activated microglia

Cited by 19 publications

References 39 publications

Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia

Aldosterone exerts anti-inflammatory effects on LPS stimulated microglia

The cancer-associated meprin β variant G32R provides an additional activation site and promotes cancer cell invasion

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

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