Microglial Depletion with Clodronate Liposomes Increases Proinflammatory Cytokine Levels, Induces Astrocyte Activation, and Damages Blood Vessel Integrity

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

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MSCs derived from amniotic fluid and umbilical cord require different administration schemes and exert different curative effects on different tissues in rats with CLP-induced sepsis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02218-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rui Chen ◽

Yingjun Xie ◽

Xuan Zhong ◽

Fei Chen ◽

Yu Gong ◽

...

Keyword(s):

Survival Rate ◽

Amniotic Fluid ◽

Umbilical Cord ◽

Proinflammatory Cytokine ◽

Disease Model ◽

Animal Experiments ◽

Cytokine Levels ◽

Liver And Kidney ◽

Two Phases ◽

Different Tissues

Abstract Background Mesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs). Although the therapeutic effect of MSCs on sepsis is already known, researchers have not determined whether the cells from different sources require different therapeutic schedules or exert different curative effects. We assessed the biofunction of the administration of AF-MSCs and UC-MSCs in rats with caecal ligation and puncture (CLP)-induced sepsis. Methods CLP was used to establish a disease model of sepsis in rats, and intravenous tail vein administration of AF-MSCs and UC-MSCs was performed to treat sepsis at 6 h after CLP. Two phases of animal experiments were implemented using MSCs harvested in saline with or without filtration. The curative effect was measured by determining the survival rate. Further effects were assessed by measuring proinflammatory cytokine levels, the plasma coagulation index, tissue histology and the pathology of the lung, liver and kidney. Results We generated rats with medium-grade sepsis with a 30–40% survival rate to study the curative effects of AF-MSCs and UC-MSCs. MSCs reversed CLP-induced changes in proinflammatory cytokine levels and coagulation activation. MSCs ameliorated CLP-induced histological and pathological changes in the lung, liver and kidney. AF-MSCs and UC-MSCs functioned differently in different tissues; UC-MSCs performed well in reducing the upregulation of inflammatory cytokine levels in the lungs and inhibiting the inflammatory cell infiltration into the liver capsule, while AF-MSCs performed well in inhibiting cell death in the kidneys and reducing the plasma blood urea nitrogen (BUN) level, an indicator of renal function. Conclusions Our studies suggest the safety and efficacy of AF-MSCs and UC-MSCs in the treatment of CLP-induced sepsis in rats and show that the cells potentially exert different curative effects on the main sepsis-affected tissues.

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Correction to: Cadmium exposure alters steroid receptors and proinflammatory cytokine levels in endothelial cells in vitro: a potential mechanism of endocrine disruptor atherogenic effect

Journal of Endocrinological Investigation ◽

10.1007/s40618-018-0994-x ◽

2018 ◽

Vol 42 (6) ◽

pp. 741-741 ◽

Cited By ~ 1

Author(s):

S. Fittipaldi ◽

V. M. Bimonte ◽

A. Soricelli ◽

A. Aversa ◽

A. Lenzi ◽

...

Keyword(s):

Endothelial Cells ◽

Proinflammatory Cytokine ◽

Endocrine Disruptor ◽

Steroid Receptors ◽

Cadmium Exposure ◽

Potential Mechanism ◽

Cytokine Levels

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Active and Passive Coping Strategies: Comparing Psychological Distress, Cortisol, and Proinflammatory Cytokine Levels in Breast Cancer Survivors

Clinical Journal of Oncology Nursing ◽

10.1188/19.cjon.583-590 ◽

2019 ◽

Vol 23 (6) ◽

pp. 583-590 ◽

Cited By ~ 1

Author(s):

Joana Perez-Tejada ◽

Larraitz Garmendia ◽

Ainitze Labaka ◽

Oscar Vegas ◽

Eneritz Gómez-Lazaro ◽

...

Keyword(s):

Breast Cancer ◽

Psychological Distress ◽

Cancer Survivors ◽

Coping Strategies ◽

Proinflammatory Cytokine ◽

Breast Cancer Survivors ◽

Passive Coping ◽

Cytokine Levels

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Dietary Fat Intake and Proinflammatory Cytokine Levels in Patients With Heart Failure

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2005.06.434 ◽

2005 ◽

Vol 11 (8) ◽

pp. 613-618 ◽

Cited By ~ 40

Author(s):

Terry A. Lennie ◽

Misook L. Chung ◽

Diane L. Habash ◽

Debra K. Moser

Keyword(s):

Heart Failure ◽

Dietary Fat ◽

Proinflammatory Cytokine ◽

Fat Intake ◽

Dietary Fat Intake ◽

Patients With Heart Failure ◽

Cytokine Levels

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NRF2 -617 C/A Polymorphism Impacts Proinflammatory Cytokine Levels, Survival, and Transplant-Related Mortality After Hematopoietic Stem Cell Transplantation in Adult Patients Receiving Busulfan-Based Conditioning Regimens

Frontiers in Pharmacology ◽

10.3389/fphar.2020.563321 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jingjing Huang ◽

Chenxia Hao ◽

Ziwei Li ◽

Ling Wang ◽

Jieling Jiang ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Clinical Outcomes ◽

Cell Transplantation ◽

Proinflammatory Cytokine ◽

Hematopoietic Stem ◽

Cytokine Levels ◽

Conditioning Regimens ◽

Related Mortality

Busulfan (BU) is widely used in conditioning regimens prior to hematopoietic stem cell transplantation (HSCT). The exposure-escalated BU directed by therapeutic drug monitoring (TDM) is extremely necessary for the patients with high-risk hematologic malignancies in order to diminish relapse, but it increases the risk of drug-induced toxicity. BU exposure, involved in the glutathione- (GSH-) glutathione S-transferases (GSTs) pathway and proinflammatory response, is associated with clinical outcomes after HSCT. However, the expression of genes in the GSH-GSTs pathway is regulated by NF-E2-related factor 2 (Nrf2) that can also alleviate inflammation. In this study, we evaluated the influence of NRF2 polymorphisms on BU exposure, proinflammatory cytokine levels, and clinical outcomes in HSCT patients. A total of 87 Chinese adult patients receiving twice-daily intravenous BU were enrolled. Compared with the patients carrying wild genotypes, those with NRF2 -617 CA/AA genotypes showed higher plasma interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α levels, poorer overall survival (OS; RR = 3.91), and increased transplant-related mortality (TRM; HR = 4.17). High BU exposure [area under the concentration-time curve (AUC) > 9.27 mg/L × h)] was related to BU toxicities. Furthermore, NRF2 -617 CA/AA genotypes could significantly impact TRM (HR = 4.04; p = 0.0142) and OS (HR = 3.69; p = 0.0272) in the patients with high BU AUC. In vitro, we found that high exposure of endothelial cell (EC) to BU, in the absence of Nrf2, elicited the hyperstimulation of NF-κB-p65, accompanied with the elevated secretion of proinflammatory cytokines, and led to EC death. These results showed that NRF2 -617 CA/AA genotypes, correlated with high proinflammatory cytokine levels, could predict inferior outcomes in HSCT patients with high BU AUC. Thus, NRF2 -617 CA/AA genotyping combined with TDM would further optimize personalized BU dosing for sufficient efficacy and safety endpoint.

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