Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells

2000 ◽  
Vol 279 (5) ◽  
pp. G918-G924 ◽  
Author(s):  
Sylvia L. F. Pender ◽  
Jessica J. Quinn ◽  
Ian R. Sanderson ◽  
Thomas T. MacDonald
Keyword(s):  
Mrna Expression ◽  
Intestinal Inflammation ◽  
Trichostatin A ◽  
Mesenchymal Cells ◽  
Rt Pcr ◽  
Nutritional Factors ◽  
Inflammatory Conditions ◽  
Factor Α ◽  
Triton X ◽  
Necrosis Factor

Nutritional factors and resident bacteria participate in the pathogenesis of intestinal inflammation. However, the ways in which bacteria and complex diets might modulate matrix metalloproteinase (MMP) production are unknown. We hypothesized that butyrate might enhance production of MMPs, thus amplifying their response to signals in inflammatory conditions. Human mesenchymal cells were incubated with butyrate and then stimulated with cytokines. MMPs and inhibitors were studied by Western blotting and quantitative RT-PCR. Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. We showed that butyrate selectively enhanced the protein production and mRNA expression of stromelysin-1 in tumor necrosis factor-α- or interleukin-1β-stimulated mesenchymal cells. Butyrate alone did not induce any change in MMP production or mRNA expression. It increased the acetylation of histones in mesenchymal cells. Furthermore, acetylation of histones (induced by trichostatin A) reproduced the effects of butyrate. Although butyrate is a major source of nutrient for the colonic epithelial cells, it modulates intestinal inflammation through the secretion of stromelysin-1 in stimulated stromal cells via the inhibition of histone deacetylase.

Granulomas in Diagnostic Biopsies Associated With High Risk of Crohn’s Complications—But May Be Preventable

2021 ◽  
Author(s):  
Lindsey S Lawrence ◽  
Amer Heider ◽  
Andrew A M Singer ◽  
Haley C Neef ◽  
Jeremy Adler
Keyword(s):  
Intestinal Inflammation ◽  
Perianal Fistula ◽  
Granulomatous Inflammation ◽  
Clinical Information ◽  
Increased Risk ◽  
Tnf Α ◽  
Pathology Reports ◽  
Factor Α ◽  
Necrosis Factor ◽  
Reduced Risk

Abstract Background Granulomatous intestinal inflammation may be associated with aggressive Crohn’s disease (CD) behavior. However, this has not been confirmed, and it is unknown if associated disease complications are preventable. Methods This is a retrospective cohort of patients younger than 21 years at CD diagnosis (November 1, 2005 to November 11, 2015). Clinical information was abstracted, including dates of starting medications and the timing of perianal fistula or stricture development, if any. Diagnostic pathology reports were reviewed, and a subset of biopsy slides were evaluated by a blinded pathologist. Patients were excluded if perianal fistula or stricture developed within 30 days after CD diagnosis. Medications were included in analyses only if started >90 days before development of perianal fistula or stricture. Results In total, 198 patients were included. Half (54%) had granulomas at diagnosis. Granulomas were associated with a greater than 3-fold increased risk of perianal fistula (hazard ration [HR] = 3.24; 95% confidence interval CI], 1.40–7.48). Immunomodulator and anti-tumor necrosis factor-α (anti-TNF) therapy were associated with 90% (HR, = 0.10; 95% CI, 0.03–0.42) and 98% (HR, = 0.02; 95% CI, 0.01–0.10) reduced risk of perianal fistula, respectively. Patients with granulomatous inflammation preferentially responded to anti-TNF therapy with reduced risk of perianal fistula. The presence of granulomas was not associated with risk of stricture. Immunomodulator and anti-TNF therapy were associated with 96% (HR, = 0.04; 95% CI, 0.01–0.22) and 94% (HR, = 0.06; 95% CI, 0.02–0.20) reduced risk of stricture, respectively. Conclusions Granulomas are associated with increased risk of perianal fistula but not stricture. Steroid sparing therapies seem to reduce the risk of both perianal fistula and stricture. For those with granulomas, anti-TNF-α therapy greatly reduced the risk of perianal fistula development, whereas immunomodulators did not.

scholarly journals Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 530 ◽  
Author(s):  
Eugenie Mussard ◽  
Sundy Jousselin ◽  
Annabelle Cesaro ◽  
Brigitte Legrain ◽  
Eric Lespessailles ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quantitative Polymerase Chain Reaction ◽  
Andrographis Paniculata ◽  
Ros Production ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Dichlorofluorescein Diacetate ◽  
Polymerase Chain ◽  
Factor Α ◽  
Necrosis Factor

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

scholarly journals Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 539
Author(s):  
Bahez Gareb ◽  
Antonius T. Otten ◽  
Henderik W. Frijlink ◽  
Gerard Dijkstra ◽  
Jos G. W. Kosterink
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Genetically Modified Organisms ◽  
Intestinal Inflammation ◽  
Systemic Exposure ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14

2001 ◽  
Vol 280 (1) ◽  
pp. L58-L68 ◽  
Author(s):  
Ulrich Maus ◽  
Susanne Herold ◽  
Heidrun Muth ◽  
Regina Maus ◽  
Leander Ermert ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Blood Monocytes ◽  
Blood Leukocytes ◽  
Alveolar Air ◽  
Inflammatory Conditions ◽  
Air Space ◽  
Factor Α ◽  
Necrosis Factor

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-α message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are “primed” for enhanced responsiveness to endotoxin with increased cytokine expression.

Cytokine treatment increases arginine metabolism and uptake in bovine pulmonary arterial endothelial cells

2001 ◽  
Vol 281 (5) ◽  
pp. L1232-L1239 ◽  
Author(s):  
Leif D. Nelin ◽  
Heather E. Nash ◽  
Louis G. Chicoine
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Cationic Amino Acid ◽  
Cytokine Treatment ◽  
Nitrite Production ◽  
Urea Production ◽  
Pulmonary Arterial ◽  
Factor Α ◽  
Arterial Endothelial Cells ◽  
Necrosis Factor

l-Arginine (l-Arg) is metabolized to nitric oxide (NO) by NO synthase (NOS) or to urea by arginase (AR). l-Arg is transported into bovine pulmonary arterial endothelial cells (BPAECs) by cationic amino acid transporter-2 (CAT-2). We hypothesized that cytokine treatment would increase l-Arg metabolism and increase CAT-2 mRNA expression. BPAECs were incubated for 24 h in medium (control) or medium with lipopolysaccharide and tumor necrosis factor-α (L-T). L-T increased nitrite production (3.1 ± 0.4 nmol/24 h vs. 1.8 ± 0.1 nmol/24 h for control; P< 0.01) and urea production (83.5 ± 29.5 nmol/24 h vs. 17.8 ± 8.6 nmol/24 h for control; P < 0.05). L-T-treated BPAECs had greater endothelial and inducible NOS mRNA expression compared with control cells. Increasing the medium l-Arg concentration resulted in increased nitrite and urea production in both the control and the L-T-treated BPAECs. L-T treatment resulted in measurable CAT-2 mRNA. L-T increasedl-[3H]Arg uptake (5.78 ± 0.41 pmol vs. 4.45 ± 0.10 pmol for control; P < 0.05). In summary, L-T treatment increased l-Arg metabolism to both NO and urea in BPAECs and resulted in increased levels of CAT-2 mRNA. This suggests that induction of NOS and/or AR is linked to induction of CAT-2 in BPAECs and may represent a mechanism for maintainingl-Arg availability to NOS and/or AR.

Mechanisms and implications of phosphoinositide 3-kinase δ in promoting neutrophil trafficking into inflamed tissue

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3448-3456 ◽  
Author(s):  
Kamal D. Puri ◽  
Teresa A. Doggett ◽  
Jason Douangpanya ◽  
Yonghao Hou ◽  
William T. Tino ◽  
...  
Keyword(s):  
Cell Attachment ◽  
Catalytic Subunit ◽  
Akt Phosphorylation ◽  
Inflammatory Conditions ◽  
Migration Assays ◽  
And Migration ◽  
Phosphoinositide 3 Kinase ◽  
Factor Α ◽  
Necrosis Factor

Abstract The phosphoinositide 3-kinase (PI3K) catalytic subunit p110δ is expressed in neutrophils and is thought to play a role in their accumulation at sites of inflammation by contributing to chemoattractant-directed migration. We report here that p110δ is present in endothelial cells and participates in neutrophil trafficking by modulating the proadhesive state of these cells in response to tumor necrosis factor α (TNFα). Specifically, administration of the selective inhibitor of PI3Kδ, IC87114, to animals reduced neutrophil tethering to and increased rolling velocities on cytokine-activated microvessels in a manner similar to that observed in mice deficient in p110δ. These results were confirmed in vitro as inhibition of this isoform in endothelium, but not neutrophils, diminished cell attachment in flow. A role for PI3Kδ in TNFα-induced signaling is demonstrated by a reduction in Akt-phosphorylation and phosphatidylinositol-dependent kinase 1 (PDK1) enzyme activity upon treatment of this cell type with IC87114. p110δ expressed in neutrophils also contributes to trafficking as demonstrated by the impaired movement of these cells across inflamed venules in animals in which this catalytic subunit was blocked or genetically deleted, results corroborated in transwell migration assays. Thus, PI3Kδ may be a reasonable therapeutic target in specific inflammatory conditions as blockade of its activity reduces neutrophil influx into tissues by diminishing their attachment to and migration across vascular endothelium. (Blood. 2004;103:3448-3456)

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