scholarly journals Immunoregulatory Effects of Somatic Extract of Toxocara canis on Airway Inflammations in Murine Model

2020 ◽  
Author(s):  
Milad BADRI ◽  
Fatemeh GHAFFARIFAR ◽  
Zuhair M. HASSAN ◽  
Abdolhossein DALIMI ◽  
Hélder CORTES
Keyword(s):  
Murine Model ◽  
Lavage Fluid ◽  
Toxocara Canis ◽  
Inhibitory Effect ◽  
Cell Number ◽  
Control Group ◽  
Tnf Α ◽  
Isolated Lung ◽  
Somatic Extract

Background: The immunomodulatory role of many parasites is well-documented. The current study designed to assess the immunoregulatory effects of the somatic extract (SE) of Toxocara canis on murine model of airway inflammations. Methods: The experiment was performed in department of parasitology of Tarbiat Modares University, Tehran, Iran from November 2018 to May 2019. Totally 30 female BALB/c mice divided into one control group and two experimental groups (10 mice in each group). The ovalbumin (OVA) group was sensitized with OVA in alum, while the SE group was administered with SE and OVA in alum intraperitoneally. The control group was injected with PBS in alum. Then, SE and OVA groups were intranasally challenged with OVA for three consecutive days and the control group encountered with PBS at the same time. One day after the last challenge, real-time PCR and histopathology survey were conducted on isolated lung tissues. Results: The gene expression of IL-25, IL-33, TNF-α and TLR-4 in SE group was significantly lower than OVA group (P<0.05). The level of IL-10, TGF-β and IFN-γ were considerably higher than the OVA group (P<0.05). The inflammation was reduced in SE group, as the total cell number of bronchoalveolar lavage fluid was less than OVA group. Based on the histopathology findings the inflammation was decreased in SE group compared to the OVA group. Conclusion: Although, an inhibitory effect of SE of T. canis on airway inflammations was detected, there is still a long way ahead regarding the indication of the precise mechanisms.

scholarly journals Mibefradil and Flunarizine, Two T-Type Calcium Channel Inhibitors, Protect Mice against Lipopolysaccharide-Induced Acute Lung Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Limei Wan ◽  
Weibin Wu ◽  
Shunjun Jiang ◽  
Shanhe Wan ◽  
Dongmei Meng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Calcium Channel ◽  
Lavage Fluid ◽  
Cell Number ◽  
Effector Cells ◽  
Potent Inhibition ◽  
Tnf Α ◽  
Calcium Channel Inhibitors

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

scholarly journals Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianwei Zhang ◽  
Lei Han ◽  
Feng Chen
Keyword(s):  
Inflammatory Response ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Mapk Pathway ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Tnf Α

Abstract Background Let-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP. Methods The expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6. Results Let-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP. Conclusion We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.

scholarly journals Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Stem Cell ◽  
Inflammatory Response ◽  
Murine Model ◽  
Licorice Root ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Stem Cell Markers ◽  
Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

scholarly journals Grain dust-induced lung inflammation is reduced byRhodobacter sphaeroidesdiphosphoryl lipid A

1998 ◽  
Vol 274 (1) ◽  
pp. L26-L31 ◽  
Author(s):  
Paul J. Jagielo ◽  
Timothy J. Quinn ◽  
Nilofer Qureshi ◽  
David A. Schwartz
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Lipid A ◽  
Partial Agonist ◽  
Inhibitory Effect ◽  
Sterile Saline ◽  
Endotoxin Activity ◽  
Tnf Α ◽  
Grain Dust

To further determine the importance of endotoxin in grain dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides (RsDPLA) as a partial agonist of grain dust-induced airway inflammation. RsDPLA is a relatively inactive compound compared with lipid A derived from Escherichia coli (LPS) and has been demonstrated to act as a partial agonist of LPS-induced inflammation. To assess the potential stimulatory effect of RsDPLA in relation to LPS, we incubated THP-1 cells with RsDPLA (0.001–100 μg/ml), LPS (0.02 μg endotoxin activity/ml), or corn dust extract (CDE; 0.02 μg endotoxin activity/ml). Incubation with RsDPLA revealed a tumor necrosis factor (TNF)-α stimulatory effect at 100 μg/ml. In contrast, incubation with LPS or CDE resulted in TNF-α release at 0.02 μg/ml. Pretreatment of THP-1 cells with varying concentrations of RsDPLA before incubation with LPS or CDE (0.02 μg endotoxin activity/ml) resulted in a dose-dependent reduction in the LPS- or CDE-induced release of TNF-α with concentrations of RsDPLA of up to 10 μg/ml but not at 100 μg/ml. To further understand the role of endotoxin in grain dust-induced airway inflammation, we utilized the unique LPS inhibitory property of RsDPLA to determine the inflammatory response to inhaled CDE in mice in the presence of RsDPLA. Ten micrograms of RsDPLA intratracheally did not cause a significant inflammatory response compared with intratracheal saline. However, pretreatment of mice with 10 μg of RsDPLA intratracheally before exposure to CDE (5.4 and 0.2 μg/m3) or LPS (7.2 and 0.28 μg/m3) resulted in significant reductions in the lung lavage concentrations of total cells, neutrophils, and specific proinflammatory cytokines compared with mice pretreated with sterile saline. These results confirm the LPS-inhibitory effect of RsDPLA and support the role of endotoxin as the principal agent in grain dust causing airway inflammation.

Lipid peroxidation and antielastase activity in the lung under oxidant stress: role of antioxidant defenses

1991 ◽  
Vol 70 (4) ◽  
pp. 1456-1462 ◽  
Author(s):  
V. Mohsenin
Keyword(s):  
Lipid Peroxidation ◽  
Oxidant Stress ◽  
Lavage Fluid ◽  
Conjugated Dienes ◽  
Antioxidant Defenses ◽  
Vitamin Supplementation ◽  
Control Group ◽  
Early Event ◽  
Lipid Peroxidation Products

The role of lipid peroxidation in the inactivation of alpha 1-protease inhibitor (alpha 1-PI) in the alveolar lining fluid of human subjects has been examined under oxidant stress. Exposure to nitrogen dioxide (NO2) at 4 ppm for 3 h resulted in a significant increase in the amount of lipid peroxidation products in the alveolar lining fluid, with conjugated dienes the predominant species. Four-week supplementation with vitamins C and E before NO2 exposure markedly decreased the levels of conjugated dienes (control 804 +/- 103 pmol/micrograms total phospholipids vs. vitamin-supplemented 369 +/- 58, P = 0.003). Malondialdehydes, although detectable in the lavage fluid, contributed little to the total amount of lipid peroxidation products, and the levels were comparable in both groups. NO2 exposure in the absence of vitamin supplementation caused a significant decrease in the elastase inhibitory capacity (EIC) of the alveolar lining fluid in the control group but not in the vitamin-supplemented group [control 3.67 +/- 0.32 micrograms alpha 1-PI/micrograms porcine pancreatic elastase (PPE) vs. vitamin-supplemented 2.75 +/- 0.17, P less than 0.03]. The vitamin-supplemented group had a lower level of conjugated dienes and a higher EIC. Conversely, the control group had higher levels of conjugated dienes and a lower EIC in their lavage fluid. These studies demonstrate that lipid peroxidation occurs as an early event during oxidant exposure in the lungs of normal subjects. The appearance of lipid peroxidation products in the lavage fluid is associated with a decrease in the EIC of the alveolar lining fluid. Vitamins C and E diminish lipid peroxidation and preserve the EIC of the lower respiratory tract fluid during oxidant stress.

The Effect of Acupuncture on Proinflammatory Cytokine Production in Patients with Chronic Headache: A Preliminary Report

2003 ◽  
Vol 31 (06) ◽  
pp. 945-954 ◽  
Author(s):  
Hyun-Ja Jeong ◽  
Seung-Heon Hong ◽  
Yong-Che Nam ◽  
Hee-Sook Yang ◽  
Yeoung-Su Lyu ◽  
...  
Keyword(s):  
Chronic Headache ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Acupuncture Treatment ◽  
Clinical Signs ◽  
Inhibitory Effect ◽  
Acute Stage ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α

Acupuncture has been widely used as a treatment for various conditions like headache and stroke, especially in Asian countries such as Korea and China. But few scientific investigations have been carried out. The aim of the present study is to investigate the effect of acupuncture on the production of inflammatory cytokines in patients with chronic headache (CH). Patients with CH were treated with acupuncture during the acute stage. Clinical signs of CH disappeared markedly after three months of treatment with acupuncture. Peripheral blood mononuclear cells obtained from a normal group and those from the patients with CH, before and after treatment with acupuncture, were cultured for 24 hours in the presence or absence of lipopolysaccharide (LPS). The amount of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS culture supernatant was significantly increased in the patients with CH compared to the healthy control group (p < 0.05). But those cytokines came down toward the levels of the healthy group (p < 0.05) after treatment with acupuncture, although the levels still remained elevated. Plasma cytokine levels were analyzed to evaluate any change due to acupuncture treatment. There was little difference in the levels of IL-1β or IL-6 due to the treatment with acupuncture in the patients with CH, but significantly reduced plasma levels of TNF-α were observed. These data suggest that acupuncture treatment has an inhibitory effect on pro-inflammatory cytokine production in patients with CH.

scholarly journals A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

2017 ◽  
Vol 43 (2) ◽  
pp. 644-659 ◽  
Author(s):  
Azza H. Abd Elwahab ◽  
Basma K. Ramadan ◽  
Mona F. Schaalan  ◽  
Amina M. Tolba
Keyword(s):  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Cafeteria Diet ◽  
Control Group ◽  
Albino Rats ◽  
Protective Mechanism ◽  
Alcoholic Fatty Liver ◽  
Group I ◽  
Tnf Α

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the alarmingly rising clinical problems in the 21st century with no effective drug treatment until now. Taurine is an essential amino acid in humans that proved efficacy as a non-pharmacological therapy in a plethora of diseases; however, its impact on NAFLD remains elusive. The aim of the current study is to evaluate the protective mechanism of taurine in experimental steatohepatitis induced by junk food given as cafeteria-diet (CAF-D) in male albino rats. Methods: Forty adult male albino rats of local strain between 8-10 weeks old, weighing 150 ± 20 g, were divided into four equal groups: Group I (control group), Group II (Taurine group), Group III (CAF-D for 12 weeks) and Group IV (CAF-D +Taurine). CAF-D was given in addition to the standard chow for 12 weeks, where each rat was given one piece of beef burger fried in 15 g of sunflower oil, one teaspoonful of mayonnaise, and one piece of petit pan bread, weighing 60g/ piece. In the serum, liver function tests; ALT, AST, ALP, GGT and the lipid profile; TG, TC, HDL-C added to reduced glutathione (GSH) were assessed colorimetrically, while fibroblast growth factor (FGF)-21, adiponectin & interleukin (IL)-6 via ELISA. The same technique was used for the assays of the hepatic levels of FGF-21, silent information regulator (SIRT1), malondialdehyde (MDA),IL-10, tumor necrosis factor-α (TNF-α) as well as the apoptotic markers; caspase-3 and B-cell lymphoma (Bcl-2). Results: The cafeteria-diet induced steatohepatitis was reflected by significantly increased body and liver weight gain, elevation of liver enzymes; ALT, AST, ALP and GGT added to the dyslipidemic panel, presented as increased TC, TG, LDL-C and decreased HDL-C levels. The steatosis-induced inflammatory milieu, marked by elevated serum levels of FGF-21, IL-6, hepatic TNF-α, as well as reduced IL-10 and adiponectin, was associated with steatosis- induced hepatic oxidative stress, reflected by increased hepatic MDA and decreased GSH levels, along with stimulated caspase-3 and decline in BcL-2 hepatic levels. These pathological disturbances were significantly ameliorated by taurine supplementation and evidenced histopathologically. The cross talk between hepatic FGF-21 and SIRT1 and their association to the induced perturbations are novel findings in this study. Taurine's efficacy in restoration of hepatic structure and function is partially via the increase in SIRT1 and associated reduction of FGF-21. Conclusion: The findings of the current study prove the protective role of taurine in NAFLD via a novel role in the amelioration of FGF-21/ SIRT1 axis, which could be considered a new therapeutic target.

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova
Keyword(s):  
Rheumatoid Arthritis ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Hypovitaminosis D ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
High Production ◽  
Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

scholarly journals Activation of angiotensin II type 2 receptor suppresses TNF-α-induced ICAM-1 via NF-кB: possible role of ACE2

2015 ◽  
Vol 309 (5) ◽  
pp. H827-H834 ◽  
Author(s):  
Liping Zhu ◽  
Oscar A. Carretero ◽  
Jiang Xu ◽  
Pamela Harding ◽  
Nithya Ramadurai ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Ang Ii ◽  
Human Coronary Artery ◽  
Activity Inhibition ◽  
Tnf Α ◽  
System Activation ◽  
Interfering Rna ◽  
Stimulation Of

ANG II type 2 receptor (AT2) and ANG I-converting enzyme 2 (ACE2) are important components of the renin-ANG system. Activation of AT2 and ACE2 reportedly counteracts proinflammatory effects of ANG II. However, the possible interaction between AT2 and ACE2 has never been established. We hypothesized that activation of AT2 increases ACE2 activity, thereby preventing TNF-α-stimulated ICAM-1 expression via inhibition of NF-κB signaling. Human coronary artery endothelial cells were pretreated with AT2 antagonist PD123319 (PD) or ACE2 inhibitor DX600 and then stimulated with TNF-α in the presence or absence of AT2 agonist CGP42112 (CGP). We found that AT2 agonist CGP increased both ACE2 protein expression and activity. This effect was blunted by AT2 antagonist PD. ICAM-1 expression was very low in untreated cells but greatly increased by TNF-α. Activation of AT2 with agonist CGP or with ANG II under concomitant AT1 antagonist reduced TNF-α-induced ICAM-1 expression, which was reversed by AT2 antagonist PD or ACE2 inhibitor DX600 or knockdown of ACE2 with small interfering RNA. AT2 activation also suppressed TNF-α-stimulated phosphorylation of inhibitory κB (p-IκB) and NF-κB activity. Inhibition of ACE2 reversed the inhibitory effect of AT2 on TNF-α-stimulated p-IκB and NF-κB activity. Our findings suggest that stimulation of AT2 reduces TNF-α-stimulated ICAM-1 expression, which is partly through ACE2-mediated inhibition of NF-κB signaling.

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