scholarly journals Macrophage Populations and Expression of Regulatory Inflammatory Factors in Hepatic Macrophage-depleted Rat Livers under Lipopolysaccharide (LPS) Treatment

2018 ◽  
Vol 46 (5) ◽  
pp. 540-552 ◽  
Author(s):  
Munmun Pervin ◽  
Mohammad Rabiul Karim ◽  
Mizuki Kuramochi ◽  
Takeshi Izawa ◽  
Mitsuru Kuwamura ◽  
...  
Keyword(s):  
Low Dose ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
Related Factors ◽  
Macrophage Activity ◽  
Hepatic Macrophages ◽  
Tnf Α ◽  
Macrophage Populations ◽  
Rat Livers ◽  
Lps Treatment

To investigate the significance of the appearance of hepatic macrophages and expression of inflammatory factors in normal and macrophage-depleted livers, hepatic macrophages were depleted with liposome (Lipo)-encapsulated clodronate (CLD; 50 mg/kg, i.v.) followed by lipopolysaccharide (LPS) administration (0.1 mg/kg, i.p.) in F344 rats (CLD + LPS). Vehicle control rats (Lipo + LPS) received empty-Lipo before LPS. The low dose of LPS did not result in microscopic changes in the liver in either treatment group but did modulate M1 and M2 macrophage activity in Lipo + LPS rats without altering repopulating hepatic macrophages in CLD + LPS rats. LPS treatment in Lipo + LPS rats dramatically increased the M1 (IL-1β, IL-6, TNF-α, and MCP-1) but not M2 macrophage-related factors (IL-4 and CSF-1) compared to CLD + LPS rats. In the CLD + LPS rats, the M2 macrophage-related factors IL-4 and CSF-1 were elevated. In conclusion, low-dose LPS activated hepatic macrophages in rat livers without causing liver injury or stimulating repopulating hepatic macrophages. These data suggest that LPS may alter the liver microenvironment by modulating M1 or M2 macrophage-related inflammatory mediators and macrophage-based hepatotoxicity.

scholarly journals Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Low Dose ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

Apoptosis perturbations and expression of regulatory inflammatory factors in cisplatin-depleted rat livers under l-arginine protection

2019 ◽  
Vol 97 (5) ◽  
pp. 359-369 ◽  
Author(s):  
Rehab M. El-Sayed ◽  
Hebatalla I. Ahmed ◽  
Abd El-Lateef S. Abd El-Lateef ◽  
Azza A. Ali
Keyword(s):  
Liver Function ◽  
Hepatic Injury ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Tnf Α ◽  
Apoptotic Marker ◽  
Apoptosis Markers ◽  
Anti Inflammatory ◽  
Rat Livers ◽  
Inflammatory Effect

Hepatic injury is one of the most common complications associated with cisplatin (CIS) use. Recently, liver protection lines are being discovered to stop the hepatic cell death due to inflammatory and apoptotic perturbations. l-arginine has protective effects in several models of liver injury. This study was designed to investigate the possible protective effect of l-arginine against CIS-induced acute hepatic injury in rats. Rats were divided into 4 groups: control, l-arginine, CIS, l-arginine + CIS. Liver function, oxidative stress, inflammatory cytokines, and apoptosis markers were assessed. l-arginine pretreatment protected the liver against CIS-induced toxicity as indicated by significantly alleviating the changes in liver function along with restoration of the antioxidant status. This finding was confirmed with the markedly improved pathological changes. l-arginine showed anti-inflammatory effect through the reduction of liver expression of iNOS, TNF-α, and NF-κβ, which were ameliorated to significant levels. Furthermore, l-arginine administration downregulated the liver expression of the apoptotic marker, caspase-3. The results recommend l-arginine as a hepatoprotective agent against CIS toxicity. Mostly, this hepatoprotective effect of l-arginine involved anti-inflammatory and anti-apoptotic activities.

Nickel-refining dust regulates the expression of inflammatory factors in NIH/3T3 cells

2019 ◽  
Vol 35 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Runan Qin ◽  
Yue Wang ◽  
Shengyuan Wang ◽  
Bing Xia ◽  
Rui Xin ◽  
...  
Keyword(s):  
Inflammatory Factors ◽  
Dependent Manner ◽  
3T3 Cells ◽  
Related Factors ◽  
Experimental Conditions ◽  
Tnf Α ◽  
Cox 2 ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

Nickel (Ni) is a metal known to be a human carcinogen that occupational workers can be exposed to during the process of Ni refining. We investigated the molecular mechanism of inflammation that is induced by Ni-refining dust in a factory, using concentrations of 0, 25, 50, and 100 µg/mL for 24 h and 48 h, in vitro. Quantitative real-time polymerase chain reactions (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays (ELISA) were used to detect the transcriptional expression levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that Ni-refining dust decreased the secretion of IL-6 under the experimental conditions. In contrast, Ni-refining dust activated NF-κB expression and stimulated the secretion of TNF-α, IL-1β, iNOS, and COX-2 in a dose- and time-dependent manner. To summarize, we demonstrated that exposure to Ni-refining dust can induce the expression of NF-κB in NIH/3T3 cells and the secretion of inflammation related factors. This provides a new basis for further study of the inflammatory effects of Ni-refining dust.

scholarly journals The clinical evaluation of combined detection of microcirculation, lipid metabolism, and inflammatory-related factors in the treatment of diabetic nephropathy with atorvastatin

2019 ◽  
Vol 17 ◽  
pp. 205873921984783 ◽  
Author(s):  
Haicheng Wang ◽  
Zhengfang Zhang ◽  
Jiali Sun
Keyword(s):  
Diabetic Nephropathy ◽  
Statistical Significance ◽  
Density Lipoprotein ◽  
Post Treatment ◽  
Inflammatory Factors ◽  
Control Group ◽  
Study Group ◽  
Related Factors ◽  
Tnf Α ◽  
Pre Treatment

This study was designed to analyze the effects of atorvastatin on microcirculation, blood lipids, inflammatory factors, and characteristic markers in patients with diabetic nephropathy. A total of 170 patients with diabetic nephropathy randomly divided into control and study groups with 85 patients in each group. The control group was treated with diet and lifestyle intervention, and hypoglycemic drugs. The study group was additionally treated with atorvastatin. Nitric oxide (NO), endothelin-1 (ET-1), thromboxane-2 (TXB2), 6-ketone-prostaglandin F-1α (6-Keto-PGF-1α), superoxide dismutase (SOD), total cholesterol (TC), triacylglycerols (TGs), low-density lipoprotein (LDL), high-density lipoprotein (HDL), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), homocysteine (Hcy), cystatin C (CysC), and vascular endothelial growth factor (VEGF) levels were observed for 8 weeks. Post-treatment of atorvastatin, the levels of NO, 6-Keto-PGF-1α, and SOD were significantly higher than pre-treatment in both groups, while the levels of ET-1 and TXB2 were lower than pre-treatment ( P < 0.05). The levels of NO, 6-Keto-PGF-1α, and SOD in the study group post-treatment were significantly higher ( P < 0.05) than the control group, and the levels of ET-1 and TXB2 in the study group were lower than the control group. After 8 weeks, the levels of TC, TG, and LDL were significantly lower, while the level of HDL was significantly higher in the study group. The level of TC was lower in the control group of post-treatment, while the HDL level was higher than pre-treatment ( P < 0.05). The levels of CRP, TNF-α, and IL-6 in the study group of post-treatment were significantly lower than pre-treatment comparing to the control group ( P < 0.05). There was no statistical significance ( P > 0.05) for above-mentioned indicators in control groups of pre- and post-treatment. The levels of VEGF, CysC, and Hcy in the two groups were lower than pre-treatment. Atorvastatin could effectively improve all the study parameters.

scholarly journals Dexmedetomidine reduces inflammation in mice with acute pancreatitis by inhibiting NLRP3 inflammasome and sympathetic nerve activity

2020 ◽  
Vol 19 (5) ◽  
pp. 943-947
Author(s):  
Yanjun Gao ◽  
JinHui Xie ◽  
Ruobin Liu ◽  
Yue Li ◽  
Wenjun Yan
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Sympathetic Nerve ◽  
Pancreatic Tissue ◽  
Inflammatory Factors ◽  
Blood Levels ◽  
Related Factors ◽  
Tnf Α ◽  
Net Protein

Purpose: To study the anti-inflammatory influence of dexmedetomidine (DEX) in mice with acute pancreatitis (AP), and to determine the underlying mechanism.Methods: A total of 75 healthy ICR male mice were randomly divided into control, mild acute pancreatitis (MAP), MAP+DEX, severe acute pancreatitis (SAP), and SAP+DEX groups, with 15 mice/group. Blood levels of inflammatory factors (TNF-α and IL-1β) and norepinephrine were assayed ineach group. Western blotting was used to assay the protein expressions of NLRP3 and norepinephrine transporter (NET) in the pancreatic tissue of each group.Results: The levels of inflammatory factors in the MAP+DEX group were markedly lower than those in the MAP group after 10 h of MAP induction (p < 0.01). Mice in MAP+DEX group had significantly lower expression of NLRP3 in pancreatic tissue, and significantly higher NET protein level, relative to the MAP mice. Following 10 h of SAP, concentrations of the inflammatory factors and the pancreatic expression of NLRP3 were lower in SAP+DEX-treated mice than in SAP mice, while NET protein was significantly higher in SAP mice (p < 0.01).Conclusion: DEX reduces the expressions of inflammation-related factors TNF-α and IL-1β, and inhibits inflammatory response in mice with AP via downregulation of NET protein expression via inhibition of NLRP3 and early sympathetic events. Keywords: Dexmedetomidine, NLRP3 inflammasome, Sympathetic nerve, Acute pancreatitis, Inflammatory response

scholarly journals Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

2021 ◽  
Vol 22 (13) ◽  
pp. 6717
Author(s):  
Camille Jacques ◽  
Ilaria Floris ◽  
Béatrice Lejeune
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Low Dose ◽  
Therapeutic Agents ◽  
Inflammatory Factors ◽  
The Past ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are two cytokines involved in the perpetuation of the chronic inflammation state characterizing rheumatoid arthritis (RA). Significant advances in the treatment of this pathology have been made over the past ten years, partially through the development of anti-TNF and anti-IL-1 therapies. However, major side effects still persist and new alternative therapies should be considered. The formulation of the micro-immunotherapy medicine (MIM) 2LARTH® uses ultra-low doses (ULD) of TNF-α, IL-1β, and IL-2, in association with other immune factors, to gently restore the body’s homeostasis. The first part of this review aims at delineating the pivotal roles played by IL-1β and TNF-α in RA physiopathology, leading to the development of anti-TNF and anti-IL-1 therapeutic agents. In a second part, an emphasis will be made on explaining the rationale of using multiple therapeutic targets, including both IL-1β and TNF-α in 2LARTH® medicine. Particular attention will be paid to the ULD of those two main pro-inflammatory factors in order to counteract their overexpression through the lens of their molecular implication in RA pathogenesis.

scholarly journals Changes in inflammatory factors in the Brown Norway rat model of food allergy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Qingling Zhu ◽  
Junli Wang ◽  
Jingqiu Ma ◽  
Xiaoyang Sheng ◽  
Feng Li
Keyword(s):  
Food Allergy ◽  
Intestinal Inflammation ◽  
Food Allergies ◽  
Inflammatory Factors ◽  
Brown Norway ◽  
Control Group ◽  
Related Factors ◽  
Norway Rat ◽  
Tnf Α ◽  
Experimental Group

Abstract Background The role of serum S100A8/A9 in intestinal inflammation has been confirmed, and its role in food allergy is currently being investigated. Objective To explore the levels of S100A8/A9 and inflammatory factors, including Toll-like receptors 4 (TLR4), Nuclear transcription factors (NF-κB) and Tumor necrosis factor α (TNF-α), in mild food allergies. Methods Eighty 3-week-old male Brown Norway rats were used. Forty rats were randomly assigned to the ovalbumin-sensitized experimental group, while 40 rats were assigned to the normal saline sham-sensitized control group. Body weight and length and the levels of serum ovalbumin-specific IgE (OVA-IgE), histamine, Th1-associated and Th2-associated factors, S100A8/A9 and inflammation-associated cytokines were compared. Results Through the evaluation of OVA-IgE level and Th1/Th2 balance in the experimental group, a successful IgE-mediated food allergy model was constructed. Compared with the control group, the experimental group had higher serum S100A8/A9 levels on days 21, 28, 35 and 42 (all P < 0.05); higher TLR4 levels on days 28, 35 and 42 (all P < 0.05); higher TNF-α levels on days 28, 35 and 42 (all P < 0.05); higher NF-κB levels on days 35 and 42 (all P < 0.05); and higher IL-1β and IL-6 levels on days 7 to 42 (all P < 0.05). Moreover, positive correlations were found between the serum levels of S100A8/A9 and inflammation-associated cytokines [TNF-α: r = 0.378, P = 0.039; IL-1β: r = 0.679, P = 0.000; IL-6: r = 0.590, P = 0.001]. Conclusion S100A8/A9 and inflammatory-related factors, including TLR4, NF-κB, TNF-α, IL-6 and IL-1β, is closely related to food allergies. Moreover, immune and inflammatory factors interact with each other in food allergies, which may provide insight into food allergy causes and treatments.

scholarly journals Overexpression of miR-874-3p alleviates LPS-induced apoptosis and inflammation in alveolar epithelial cell by targeting EGR3/NF-κB

2021 ◽  
Author(s):  
Huirun Yang ◽  
Yang Dong ◽  
Yan Zhou ◽  
Huajun Li
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Promoter Activity ◽  
Pediatric Patients ◽  
Inflammatory Factors ◽  
Serum Samples ◽  
Expression Levels ◽  
Over Expression ◽  
Tnf Α ◽  
Lps Treatment

Objective: MicroRNA (miRNA) is implicated in the pathogenic mechanism of pneumonia. Role of miR-874-3p in pediatric pneumonia was therefore evaluated in this study. Methods: Expression levels of miR-874-3p in the serum samples from pediatric patients with pneumonia and LPS-treated HPAEpiC were determined by RT-qPCR (reverse transcription quantitative real-time PCR). Secretion of inflammatory factors in LPS-treated HPAEpiC were determined by qRT-PCR and ELISA. Cell viability and apoptosis were evaluated by CCK8 and flow cytometry, respectively. HPAEpiC was used for the validation of binding target of miR-874-3p. Mechanism was determined by NF-κB promoter activity assay. Results: MiR-874-3p was reduced in serum samples of pediatric patients with pneumonia, and LPS treatment dose-dependently decreased miR-874-3p expression in HPAEpiC. TNF-α and IL-1β expression levels were increased in HPAEpiC post LPS treatment. Over-expression of miR-874-3p attenuated LPS-induced increase of TNF-α and IL-1β and reversed LPS-induced decrease of cell viability and increase of cell apoptosis in HPAEpiC. EGR3 (early growth response 3), increased in LPS-induced HPAEpiC, was a target gene of miR-874-3p. EGR3 over-expression reversed miR-874-3p over-expression-induced increase of cell viability, decrease of cell apoptosis, TNF-α and IL-1β in LPS-induced HPAEpiC. Over-expression of miR-874-3p reduced p65 expression and NF-κB promoter activity in LPS-induced HPAEpiC, while EGR3 over-expression reversed these suppressive effects. Conclusion: MiR-874-3p negatively regulates EGR3 expression to promote cell viability and inhibit apoptosis as well as inflammation in LPS-treated HPAEpiC via suppression of NF-κB pathway, suggesting a potential therapeutic strategy for pneumonia.

scholarly journals Depletion of Hepatic Macrophages Aggravates Liver Lesions Induced in Rats by Thioacetamide (TAA)

2016 ◽  
Vol 44 (2) ◽  
pp. 246-258 ◽  
Author(s):  
Hossain M. Golbar ◽  
Takeshi Izawa ◽  
Kavindra K. Wijesundera ◽  
Alexandra Bondoc ◽  
Anusha H. Tennakoon ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Inflammatory Factors ◽  
Coagulation Necrosis ◽  
Dystrophic Calcification ◽  
M2 Macrophages ◽  
Related Factors ◽  
Hepatic Macrophages

Hepatic macrophages play crucial roles in hepatotoxicity. We investigated immunophenotypes of macrophages in liver injury induced in rats by thioacetamide (TAA; 300 mg/kg, intraperitoneal) after hepatic macrophage depletion; hepatic macrophages were depleted by liposomal clodronate (CLD; 10 ml/kg, i.v.) one day before TAA injection. Samples were obtained on post-TAA injection days 0, 1, 2, 3, 5, and 7. TAA injection induced coagulation necrosis of hepatocytes on days 1 through 3 and subsequent reparative fibrosis on days 5 and 7 in the centrilobular area, accompanied by increased numbers of M1 macrophages (expressing cluster of differentiation [CD]68 and major histocompatibility complex class II) and M2 macrophages (expressing CD163 and CD204) mainly on days 1 through 3. TAA + CLD treatment markedly decreased the numbers of M1 and M2 macrophages mainly on days 1 through 3; CD163+ Kupffer cells were most sensitive to CLD depletion. In TAA + CLD–treated rats, interestingly, coagulation necrosis of hepatocytes was prolonged with more increased levels of hepatic enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase) to TAA-treated rats; reparative fibrosis was incomplete and replaced by dystrophic calcification in the injured area, indicating the aggravated damage. Furthermore, in TAA + CLD–treated rats, inflammatory factors (monocyte chemoattractant protein [MCP]-1, interferon-γ, tumor necrosis factor-α, and interleukin-10) and fibrosis-related factors (transforming growth factor-β1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1) were decreased at messenger RNA levels, indicating abnormal macrophage functions. It was clearly demonstrated that hepatic macrophages have important roles in tissue damage and remodeling in hepatotoxicity.

scholarly journals Triptolide Inhibits the Activation of NLRP3 Inflammasome by Inhibiting NF-κB Pathway and Improves Myocardial Fibrosis

2021 ◽  
Author(s):  
Jianyao Shen ◽  
Hailiang Ma ◽  
Chaoquan Wang
Keyword(s):  
Myocardial Fibrosis ◽  
Nlrp3 Inflammasome ◽  
Subcutaneous Injection ◽  
Tissue Injury ◽  
Myocardial Cell ◽  
Inflammatory Factors ◽  
Inflammasome Activation ◽  
Related Factors ◽  
Nlrp3 Inflammasome Activation ◽  
Tnf Α

Abstract ObjectiveTriptolide (TPL) is identified to be involved in the treatment for myocardial fibrosis (MF). This study investigated the mechanism of TPL in MF in rats and observed its effect on NLRP3 inflammasome signaling pathway.Materials and MethodsThe MF rat model was established by subcutaneous injection of isoproterenol (ISO), and treated by subcutaneous injection of TPL. After modeling for 1 week, the cardiac function of rats was evaluated, including LVEF, LVFS, LVES, LVED LVIDs and LVPWs. The HMI and LVMI were measured. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM-1), and NLRP3 inflammasome factors (NLRP3, ASC, caspase-1) in rats were detected. HE staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats.ResultsLVED, LVES, LVIDs and LVPWs of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, HMI and LVMI were upregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF.ConclusionsTPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved the degree of MF in MF rats.

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