Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates

2013 ◽  
Vol 304 (10) ◽  
pp. G864-G875 ◽  
Author(s):  
Jayda Siggers ◽  
Mette V. Østergaard ◽  
Richard H. Siggers ◽  
Kerstin Skovgaard ◽  
Lars Mølbak ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Necrotizing Enterocolitis ◽  
Enteral Feeding ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Preterm Neonates ◽  
Gut Colonization ◽  
Tnf Α ◽  
Before And After ◽  
And Migration

Preterm neonates are susceptible to gastrointestinal disorders such as necrotizing enterocolitis (NEC). Maternal milk and colostrum protects against NEC via growth promoting, immunomodulatory, and antimicrobial factors. The fetal enteral diet amniotic fluid (AF), contains similar components, and we hypothesized that postnatal AF administration reduces inflammatory responses and NEC in preterm neonates. Preterm pigs (92% gestation) were delivered by caesarean section and fed parental nutrition (2 days) followed by enteral (2 days) porcine colostrum (COLOS, n = 7), infant formula (FORM, n = 13), or AF supplied before and after introduction of formula (AF, n = 10) in experiment 1, and supplied only during the enteral feeding period in experiment 2 (FORM, n = 16; AF, n = 14). The NEC score was reduced in both AF and COLOS pigs, relative to FORM, when AF was provided prior to full enteral feeding (9.9 and 7.7 compared with 17.3, P < 0.05). There was no effect of AF when provided only during enteral feeding. AF pigs showed decreased bacterial abundance in colon and intestinal inflammation-related genes (e.g., TNF-α, IL-1α, IL-6, NOS) were downregulated, relative to FORM pigs with NEC. Anti-inflammatory properties of AF were supported by delayed maturation and decreased TNF-α production in murine dendritic cells, as well as increased proliferation and migration, and downregulation of IL-6 expression in intestinal cells (IEC-6, IPEC-J2). Like colostrum, AF may reduce NEC development in preterm neonates by suppressing the proinflammatory responses to enteral formula feeding and gut colonization when provided before the onset of NEC.

scholarly journals Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1726
Author(s):  
Ilse H. de Lange ◽  
Charlotte van Gorp ◽  
Laurens D. Eeftinck Schattenkerk ◽  
Wim G. van Gemert ◽  
Joep P. M. Derikx ◽  
...  
Keyword(s):  
Systematic Review ◽  
Necrotizing Enterocolitis ◽  
Enteral Feeding ◽  
Intestinal Inflammation ◽  
Immune Defense ◽  
Microbial Colonization ◽  
Effective Prevention ◽  
Pathophysiological Mechanisms ◽  
Gut Colonization ◽  
Feeding Interventions

Necrotizing enterocolitis (NEC), which is characterized by severe intestinal inflammation and in advanced stages necrosis, is a gastrointestinal emergency in the neonate with high mortality and morbidity. Despite advancing medical care, effective prevention strategies remain sparse. Factors contributing to the complex pathogenesis of NEC include immaturity of the intestinal immune defense, barrier function, motility and local circulatory regulation and abnormal microbial colonization. Interestingly, enteral feeding is regarded as an important modifiable factor influencing NEC pathogenesis. Moreover, breast milk, which forms the currently most effective prevention strategy, contains many bioactive components that are known to support neonatal immune development and promote healthy gut colonization. This systematic review describes the effect of different enteral feeding interventions on the prevention of NEC incidence and severity and the effect on pathophysiological mechanisms of NEC, in both experimental NEC models and clinical NEC. Besides, pathophysiological mechanisms involved in human NEC development are briefly described to give context for the findings of altered pathophysiological mechanisms of NEC by enteral feeding interventions.

Abstract 187: Regulation of Vascular Smooth Muscle Cell (VSMC) Inflammation and Migration by the Pro-resolving Lipid Mediator Maresin-1 (mar1)

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Anuran Chatterjee ◽  
Robert Toy ◽  
Giorgio Mottola ◽  
Mian Chen ◽  
Michael S Conte
Keyword(s):  
Actin Polymerization ◽  
Inflammatory Responses ◽  
Oxidant Stress ◽  
Lipid Mediator ◽  
Monocyte Adhesion ◽  
Inflammatory Gene Expression ◽  
New Class ◽  
Tnf Α ◽  
And Migration ◽  
Inflammatory Molecules

Introduction Resolution of acute inflammation is regulated by endogenous lipid mediators derived from polyunsaturated fatty acids such as docosahexaenoic acid (DHA), however little is known about mechanisms of resolution in vascular injury. We investigated the effects of the DHA-derived mediator Mar1 on VSMC phenotype responses. Methods Primary human VSMCs were obtained from saphenous vein. VSMC were pretreated with Mar1 (10-100nM) then exposed to TNF-α (10ng/ml), and inflammatory responses assessed using a monocyte adhesion (U937) assay, expression of cell adhesion molecules and pro-inflammatory molecules (qPCR, western blot, ELISA), and production of superoxide (DHE). VSMC migration was measured in a transwell assay with PDGF-AB as the agonist, and cyotskeletal changes were assessed by actin-phalloidin staining. Results Mar-1 (100 nM) reduced U937 adhesion to TNF-stimulated VSMC, VCAM-1, and pro-inflammatory cytokine (IL-6, IL-8) expression. Superoxide production measured by DHE fluorescence was reduced by 57% (p=0.002) and Nox4 expression was markedly attenuated (43%, p=0.01). Mar-1 (0.01-100nM) induced rapid cytoskeletal changes with increased cell area, and reduced VSMC migration (76%, p=0.004) to PDGF-AB (50ng/ml; Figure). Conclusions Mar-1 attenuates TNF-α inflammatory activation of VSMC, with reduction in pro-inflammatory gene expression, oxidant stress, and monocyte adhesion. Mar-1 reduces actin polymerization and inhibits VSMC chemotaxis to PDGF. Pro-resolving mediators may represent a new class of endogenous vascular therapeutics.

scholarly journals Differences in postprandial inflammatory responses to a ‘modern’ v. traditional meat meal: a preliminary study

2010 ◽  
Vol 104 (5) ◽  
pp. 724-728 ◽  
Author(s):  
Fatemeh Arya ◽  
Sam Egger ◽  
David Colquhoun ◽  
David Sullivan ◽  
Sebely Pal ◽  
...  
Keyword(s):  
Immune Reaction ◽  
Inflammatory Responses ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Meat Meal ◽  
Tnf Α ◽  
Before And After ◽  
Preliminary Study ◽  
New Form

A low-grade inflammatory response (‘metaflammation’) has been found to be associated with certain chronic diseases. Proposed inducers of this have been aspects of the modern lifestyle, including newly introduced foods. Plasma TAG, and the inflammatory cytokines C-reactive protein (CRP), TNF-α and IL-6 were compared in a randomised, cross-over trial using ten healthy subjects before and after eating 100 g of kangaroo, or a ‘new’ form of hybridised beef (wagyu) separated by about 1 week. Postprandial levels for 1 and 2 h of TAG, IL-6 and TNF-α were significantly higher after eating wagyu compared with kangaroo (P = 0·002 for TAG at 1 h, P < 0·001 at 2 h; P < 0·001 for IL-6 and TNF-α at 1 and 2 h). CRP was significantly higher 1 h postprandially after wagyu (P = 0·011) and non-significantly higher 2 h postprandially (P = 0·090). We conclude that the metaflammatory reaction to ingestion of a ‘new’ form of hybridised beef (wagyu) is indicative of a low-grade, systemic, immune reaction when compared with lean game meat (kangaroo). Further studies using isoenergetic intake and isolating fatty acid components of meats are proposed.

scholarly journals Endothelial and inflammatory responses to acute exercise in perimenopausal and late postmenopausal women

2016 ◽  
Vol 311 (5) ◽  
pp. R841-R850 ◽  
Author(s):  
Corinna Serviente ◽  
Lisa M. Troy ◽  
Maxine de Jonge ◽  
Daniel D. Shill ◽  
Nathan T. Jenkins ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Postmenopausal Women ◽  
Acute Exercise ◽  
Inflammatory Responses ◽  
Subclinical Atherosclerosis ◽  
Inflammatory Factors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Before And After ◽  
Factor Α

Endothelial dysfunction and inflammation are characteristics of subclinical atherosclerosis and may increase through progressive menopausal stages. Evaluating endothelial responses to acute exercise can reveal underlying dysfunction not apparent in resting conditions. The purpose of this study was to investigate markers of endothelial function and inflammation before and after acute exercise in healthy low-active perimenopausal (PERI) and late postmenopausal (POST) women. Flow-mediated dilation (FMD), CD31+/CD42b− and CD62E+ endothelial microparticles (EMPs), and the circulating inflammatory factors monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), and tumor necrosis factor-α (TNF-α) were measured before and 30 min after acute exercise. Before exercise, FMD was not different between groups (PERI: 6.4 ± 0.9% vs. POST: 6.5 ± 0.8%, P = 0.97); however, after acute exercise PERI tended to improve FMD (8.5 ± 0.9%, P = 0.09), whereas POST did not (6.2 ± 0.8%, P = 0.77). Independent of exercise, we observed transient endothelial dysfunction in POST with repeated FMD measures. There was a group × exercise interaction for CD31+/CD42b− EMPs ( P = 0.04), where CD31+/CD42b− EMPs were similar before exercise (PERI: 57.0 ± 6.7 EMPs/μl vs. POST: 58.5 ± 5.3 EMPs/μl, P = 0.86) but were higher in POST following exercise (PERI: 48.2 ± 6.7 EMPs/μl vs. POST: 69.4 ± 5.3 EMPs/μl, P = 0.023). CD62E+ EMPs were lower in PERI compared with POST before exercise ( P < 0.001) and increased in PERI ( P = 0.04) but did not change in POST ( P = 0.68) in response to acute exercise. After acute exercise, MCP-1 ( P = 0.055), TNF-α ( P = 0.02), and IL-8 ( P < 0.001) were lower in PERI but only IL-8 decreased in POST ( P < 0.001). Overall, these data suggest that perimenopausal and late postmenopausal women display different endothelial and inflammatory responses to acute exercise.

scholarly journals Fidaxomicin and OP-1118 Inhibit Clostridium difficile Toxin A- and B-Mediated Inflammatory Responses via Inhibition of NF-κB Activity

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Hon Wai Koon ◽  
Jiani Wang ◽  
Caroline C. Mussatto ◽  
Christina Ortiz ◽  
Elaine C. Lee ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Human Colon ◽  
Toxin A ◽  
Primary Metabolite ◽  
Necrosis Factor Alpha ◽  
Toxin B ◽  
Content Type ◽  
Tnf Α

ABSTRACTClostridium difficilecauses diarrhea and colitis by releasing toxin A and toxin B. In the human colon, both toxins cause intestinal inflammation and stimulate tumor necrosis factor alpha (TNF-α) expression via the activation of NF-κB. It is well established that the macrolide antibiotic fidaxomicin is associated with reduced relapses ofC. difficileinfection. We showed that fidaxomicin and its primary metabolite OP-1118 significantly inhibited toxin A-mediated intestinal inflammation in micein vivoand toxin A-induced cell roundingin vitro. We aim to determine whether fidaxomicin and OP-1118 possess anti-inflammatory effects against toxin A and toxin B in the human colon and examine the mechanism of this response. We used fresh human colonic explants, NCM460 human colonic epithelial cells, and RAW264.7 mouse macrophages to study the mechanism of the activity of fidaxomicin and OP-1118 against toxin A- and B-mediated cytokine expression and apoptosis. Fidaxomicin and OP-1118 dose-dependently inhibited toxin A- and B-induced TNF-α and interleukin-1β (IL-1β) mRNA expression and histological damage in human colonic explants. Fidaxomicin and OP-1118 inhibited toxin A-mediated NF-κB phosphorylation in human and mouse intestinal mucosae. Fidaxomicin and OP-1118 also inhibited toxin A-mediated NF-κB phosphorylation and TNF-α expression in macrophages, which was reversed by the NF-κB activator phorbol myristate acetate (PMA). Fidaxomicin and OP-1118 prevented toxin A- and B-mediated apoptosis in NCM460 cells, which was reversed by the addition of PMA. PMA reversed the cytoprotective effect of fidaxomicin and OP-1118 in toxin-exposed human colonic explants. Fidaxomicin and OP-1118 inhibitC. difficiletoxin A- and B-mediated inflammatory responses, NF-κB phosphorylation, and tissue damage in the human colon.

Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine

2014 ◽  
Vol 307 (7) ◽  
pp. G689-G699 ◽  
Author(s):  
Duc Ninh Nguyen ◽  
Per T. Sangild ◽  
Mette V. Østergaard ◽  
Stine B. Bering ◽  
Dereck E. W. Chatterton
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Preterm Neonates ◽  
Epithelial Cell Line ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis ◽  
Erk Activation ◽  
Transforming Growth Factor Β2 ◽  
And Migration

A balance between pro- and anti-inflammatory signals from milk and microbiota controls intestinal homeostasis just after birth, and an optimal balance is particularly important for preterm neonates that are sensitive to necrotizing enterocolitis (NEC). We suggest that the intestinal cytokine IL-8 plays an important role and hypothesize that transforming growth factor-β2 (TGF-β2) acts in synergy with bacterial lipopolysaccharide (LPS) to control IL-8 levels, thereby supporting intestinal homeostasis. Preterm pigs were fed colostrum (containing TGF-β2) or infant formula (IF) with or without antibiotics (COLOS, n = 27; ANTI, n = 11; IF, n = 40). Intestinal IL-8 levels and NEC incidence were much higher in IF than in COLOS and ANTI pigs ( P < 0.001), but IL-8 levels did not correlate with NEC severity. Intestinal TGF-β2 levels were high in COLOS but low in IF and ANTI pigs. Based on these observations, the interplay among IL-8, TGF-β2, and LPS was investigated in a porcine intestinal epithelial cell line. TGF-β2 attenuated LPS-induced IL-6, IL-1β, and TNF-α release by reducing early ERK activation, whereas IL-8 secretion was synergistically induced by LPS and TGF-β2 via NF-κB. The TGF-β2/LPS-induced IL-8 levels stimulated cell proliferation and migration following epithelial injury, without continuous NF-κB activation and cyclooxygenase-2 expression. We suggest that a combined TGF-β2-LPS induction of IL-8 stimulates epithelial repair just after birth when the intestine is first exposed to colonizing bacteria and TGF-β2-containing milk. Moderate IL-8 levels may act to control intestinal inflammation, whereas excessive IL-8 production may enhance the damaging proinflammatory cascade leading to NEC.

scholarly journals Monocyte-derived and M1 macrophages from ankylosing spondylitis patients released higher TNF-α and expressed more IL1B in response to BzATP than macrophages from healthy subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maryam Akhtari ◽  
Seyed Jalal Zargar ◽  
Mahdi Vojdanian ◽  
Ahmadreza Jamshidi ◽  
Mahdi Mahmoudi
Keyword(s):  
Ankylosing Spondylitis ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
The Body ◽  
Protein Release ◽  
M1 Macrophages ◽  
Tnf Α ◽  
Before And After ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

AbstractMacrophages participate in the pathogenesis of ankylosing spondylitis (AS) by producing inflammatory cytokines. Extracellular adenosine triphosphate (eATP), released during cell stress, acts through purinergic receptors (P2XR and P2YR) and induces inflammatory responses. We investigated the effect of 2ʹ(3ʹ)-O-(4-benzoyl benzoyl) ATP (BzATP) (a prototypic agonist of P2X7R) on the production of inflammatory cytokines in both monocyte-generated (M2-like) and M1 macrophages from patients and controls. Macrophages were differentiated from isolated periphery-monocytes (n = 14 in each group) by macrophage colony-stimulating factor (M-CSF). Using LPS and IFN-γ, macrophages were skewed toward M1 type and were treated with BzATP. Gene expression and protein release of IL-1β, IL-23, and TNF-α were evaluated by real-time PCR and ELISA methods respectively before and after treatment. BzATP significantly increased the protein release of TNF-α and the expression of TNFA and IL1B in monocyte-generated macrophages. Besides, BzATP treatment significantly upregulated IL1B expression, reduced TNFA and IL23A expression, and TNF-α release in M1 macrophages from both groups. Monocyte-generated and M1 macrophages from AS patients released higher TNF-α and expressed more IL1B in response to the same concentration of BzATP treatment respectively. Based on our results, AS macrophages were more sensitive to BzATP treatment and responded more intensively. Besides, the diverse effects of BzATP on monocyte-derived and M1 macrophages in our study may represent the differed inflammatory properties of these two groups of macrophages in response to eATP in the body.

scholarly journals Exogenous Autoinducer-2 Rescues Intestinal Dysbiosis and Intestinal Inflammation in a Neonatal Mouse Necrotizing Enterocolitis Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan-Chun Ji ◽  
Qian Sun ◽  
Chun-Yan Fu ◽  
Xiang She ◽  
Xiao-Chen Liu ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Intestinal Inflammation ◽  
Control Group ◽  
Inflammatory Factor ◽  
Formula Milk ◽  
Autoinducer 2 ◽  
Intestinal Dysbiosis ◽  
Tnf Α ◽  
And Control ◽  
Proinflammatory Factors

Autoinducer-2 (AI-2) is believed to be a bacterial interspecies signaling molecule that plays an important role in the regulation of the physiological behaviors of bacteria. The effect of AI-2 on the process of necrotizing enterocolitis (NEC) is unknown, and the aim of this study was to study the effect of AI-2 in a mouse NEC model. C57BL/6 mouse pups were randomly divided into three groups: the control group, the NEC group, and the NEC+AI-2 (NA) group. Exogenous AI-2 (500 nM) was added to the formula milk of the NA group. The concentrations of fecal AI-2 and flora were tested. The expression of cytokines, TLR4 and NF-κB in intestinal tissue was detected. The AI-2 level was significantly decreased in the NEC group (P&lt;0.05). Compared with the NEC group, the intestinal injury scores, expression of TLR4, NF-kB, and proinflammatory factors (IL-1β, IL-6, IL-8 and TNF-α) were reduced, and expression of anti-inflammatory factor (IL-10) was increased in the NA group mice (P&lt;0.05). At the phylum level, the Proteobacteria abundance in the NA group was significantly increased, while the Bacteroidota abundance in the control group was significantly increased (P&lt;0.05). At the genus level, Helicobacter and Clostridium_sensu_stricto_1 exhibited significantly greater abundance in the NEC group than in the other two groups, while Lactobacillus had the opposite trend (P&lt;0.05). In addition, the abundances of Klebsiella, Rodentibacter and Enterococcus were significantly higher in the NA group than in the NEC and control groups (P &lt; 0.05). Exogenous AI-2 partially reverses flora disorder and decreases inflammation in an NEC mouse model.

scholarly journals Immune Protection of a Helminth Protein in the DSS-Induced Colitis Model in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Shao Rong Long ◽  
Ruo Dan Liu ◽  
Deepak Vijaya Kumar ◽  
Zhong Quan Wang ◽  
Chien-Wen Su
Keyword(s):  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Trichinella Spiralis ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Inflammatory Bowel ◽  
Potential Use ◽  
Colitis Model

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Recent clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. Reports have highlighted the potential use of helminths and their byproducts as potential treatment for IBD. In the current study, we studied the effect of a newborn larvae-specific serine protease from Trichinella spiralis (TsSp) on the host immune and inflammatory responses. A 49-kDa recombinant TsSp (rTsSp) was expressed in Escherichia coli BL21 (DE3) and purified. The cytotoxicity of rTsSp was analyzed. The immune protective effect of rTsSp was studied by using dextran sodium sulfate (DSS)-induced mouse colitis model. The result illustrated that rTsSp has no toxic effects on cells. We further demonstrated that administration of the rTsSp without the additional adjuvant before the induction of DSS-induced colitis reduced the severity of intestinal inflammation and the disease index; it suppressed macrophage infiltration, reduced TNF-α secretion, and induced IL-10 expression. Our findings suggest therapeutic potential of rTsSp on colitis by altering the effect of macrophages. Data also suggest immunotherapy with rTsSp holds promise for use as an additional strategy to positively modulate inflammatory processes involved in IBD.

scholarly journals TPL2 Is a Key Regulator of Intestinal Inflammation in Clostridium difficile Infection

2018 ◽  
Vol 86 (8) ◽  
Author(s):  
Yuanguo Wang ◽  
Shaohui Wang ◽  
Ciaran P. Kelly ◽  
Hanping Feng ◽  
Andrew Greenberg ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Gene Ablation ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Mitogen Activated Protein

ABSTRACT Tumor progression locus 2 (TPL2), a serine/threonine protein kinase, is a major inflammatory mediator in immune cells. The predominant inflammatory actions of TPL2 depend on the activation of mitogen-activated protein kinases (MAPK) and the upregulated production of the cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) in macrophages and dendritic cells in response to lipopolysaccharide (LPS). Significant increases in TNF-α, IL-6, IL-β, and IL-8 levels in patients with Clostridium difficile infection (CDI) have been reported. Both TNF-α and IL-6 have been postulated to play key roles in the systemic inflammatory response in CDI, and IL-8 is essential for the development of local intestinal inflammatory responses in CDI. The objective of this study was to elucidate the role of TPL2 in the pathogenesis of CDI. We found that TPL2 was significantly activated in human and mouse intestinal tissues upon C. difficile toxin exposure or CDI. We further demonstrated that TPL2 knockout (TPL2-KO) mice were significantly more resistant to CDI than wild-type mice, with significantly reduced production of TNF-α, IL-6, IL-1β, KC (a mouse homologue of IL-8), and myeloperoxidase (MPO) in the ceca and colons of TPL2-KO mice. Finally, we found that TPL2 inhibition by a specific inhibitor or TPL2 gene ablation significantly reduced TcdB-induced production of TNF-α, IL-6, IL-β, and KC by inhibiting the activation of p38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK). Taken together, our data suggest that TPL2 represents a potential therapeutic target for CDI treatment.

Sign in / Sign up

Export Citation Format

Share Document