Pre-treatment with α-tocopherol andTerminalia arjunaameliorates, pro-inflammatory cytokines, cardiac and apoptotic markers in myocardial infracted rats

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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Vitamin D3 controls TLR4- and TLR2-mediated inflammatory responses of endometrial cells

10.21203/rs.2.19548/v1 ◽

2019 ◽

Author(s):

Alireza Ghanavatinejad ◽

Nesa Rashidi ◽

Mahroo Mirahmadian ◽

Simin Rezania ◽

Mahdokht Mosalaei ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Vitamin D3 ◽

Inflammatory Responses ◽

Female Reproductive Tract ◽

Endometrial Stromal Cells ◽

Endometrial Cells ◽

Tnf Α ◽

Pre Treatment ◽

Tract Infections ◽

Pro Inflammatory Cytokines

Abstract Background: There is a significant association between intrauterine infection-associated inflammatory responses and such pregnancy complications as abortion and preterm labor. Here, we aimed to investigate anti-inflammatory effects of 1,25 (OH)2 D3 on pro-inflammatory cytokines secretion and expression of TLR2, TLR4 and MyD88 in endometrial stromal cells (ESCs) and whole endometrial cells (WECs). Method: WECs were treated with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) and ESCs were treated with LPS. IL-6, IL8 and TNF-α were quantified using ELISA technique. TLR2, TLR4 and MyD88 expression were assessed by RT-qPCR. TLR4 expression at the protein level was studied by Western blot technique. Results: 1,25 (OH)2 D3 significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pre-treatment increased production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pre-treatment markedly reduced LPS-induced TLR-4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pre-treated with 1,25 (OH)2 D3 before stimulation with LPS. Conclusion: 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintenance of endometrial immune homeostasis through controlling potentially harmful inflammatory responses associated with female reproductive tract infections. Key words: Vitamin D3, Endometrium, Inflammation, Toll like receptors, Pro-inflammatory cytokines

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Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

10.21203/rs.3.rs-46684/v2 ◽

2020 ◽

Author(s):

Ling Mao ◽

Ya Zhou ◽

Longqing Chen ◽

Lin Hu ◽

Shiming Liu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Survival Time ◽

Inflammatory Cytokines ◽

Mitogen Activated Protein Kinase ◽

Lps Challenge ◽

Mitogen Activated Protein ◽

Pre Treatment ◽

Pro Inflammatory Cytokines

Abstract Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4 -/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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Pre-treatment with Beta Carotene Gives Protection Against Nephrotoxicity Induced by Bromobenzene via Modulation of Antioxidant System, Pro-inflammatory Cytokines and Pro-apoptotic Factors

Applied Biochemistry and Biotechnology ◽

10.1007/s12010-019-03111-0 ◽

2019 ◽

Vol 190 (2) ◽

pp. 616-633 ◽

Cited By ~ 1

Author(s):

Priya Josson Akkara ◽

Evan Prince Sabina

Keyword(s):

Inflammatory Cytokines ◽

Antioxidant System ◽

Beta Carotene ◽

Pre Treatment ◽

Apoptotic Factors ◽

Pro Inflammatory Cytokines

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Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

Cell & Bioscience ◽

10.1186/s13578-020-00484-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ling Mao ◽

Ya Zhou ◽

Longqing Chen ◽

Lin Hu ◽

Shiming Liu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Survival Time ◽

Inflammatory Cytokines ◽

Mitogen Activated Protein Kinase ◽

Lps Challenge ◽

Mitogen Activated Protein ◽

Pre Treatment ◽

Pro Inflammatory Cytokines

Abstract Background Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4−/− mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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Methanol Extract of Chasmanthera dependens Stem Mitigates against Mechanisms Involved in Piroxicam-induced Liver Damage in Rat

Journal of Complementary and Alternative Medical Research ◽

10.9734/jocamr/2020/v10i430170 ◽

2020 ◽

pp. 16-28

Author(s):

Tijani Stephanie Abiola ◽

Olori Ogaraya David ◽

Farombi Ebenezer Olatunde

Keyword(s):

Oxidative Stress ◽

Liver Function ◽

Oral Administration ◽

Inflammatory Cytokines ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Dependent Manner ◽

Apoptotic Markers ◽

Glutamyl Transferase ◽

Pro Inflammatory Cytokines

Chasmanthera dependens has been claimed by tradition healers as a therapeutic agent in many diseases including hepatotoxicity. This study sought to evaluate the possible mechanisms involved in the hepatoprotective potential of tannin-rich extract of Chasmanthera dependens stem (TRECDS). Thirty two male Wistar rats (100- 130 g) were divided into four groups of eight rats per group labelled as group 1,2,3 and 4. The rats were treated orally for ten days consecutively. Group 1 served as control group and received normal saline, group 2 rats received 40 mg/kg piroxicam alone, groups 3-4 were treated with 40 mg/kg piroxicam and 200 and 400 mg/kg TREDS respectively concomitantly. All the experimental rats were fed with standard rat chows. Twenty four hours after, blood was collected to obtain serum; liver was excised to prepare homogenate and histology staining under pentobarbital sodium anaesthesia. Liver function test (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT)) and oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and lipid peroxidation (LPO)) biomarkers were assessed. Pro-inflammatory cytokines (tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β)) and apoptotic markers; caspase-3 (CASP-3) and caspase-9 (CAPS-9), cytochrome-c (CYT-c)) were also assessed. The results showed that piroxicam administration caused hepatic damage as was evident in the histological assessment with increased serum activities of liver function markers, levels of pro-inflammatory cytokines and apoptotic markers. TRECDS also showed significant attenuation of the oxidative stress by decreasing the LPO level and increasing the activities of SOD, CAT and GSH level. Oral administration of TRECDS also restores the morphological structure of the liver in a dose-dependent manner. Conclusion: Oral administration of TRECDS exhibited protective potential against piroxicam-induced hepatotoxicity.

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Chrysophanol Attenuates Manifestations of Immune Bowel Diseases by Regulation of Colorectal Cells and T Cells Activation In Vivo

Molecules ◽

10.3390/molecules26061682 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1682

Author(s):

Hyun-Su Lee ◽

Gil-Saeng Jeong

Keyword(s):

T Cells ◽

Oral Administration ◽

Inflammatory Cytokines ◽

Mapk Pathway ◽

Mrna Levels ◽

Immune Disorder ◽

Pre Treatment ◽

Ht 29 ◽

Pro Inflammatory Cytokines

Inflammatory bowel disease (IBD) is an immune disorder that develops due to chronic inflammation in several cells. It is known that colorectal and T cells are mainly involved in the pathogenesis of IBD. Chrysophanol is an anthraquinone family member that possesses several bioactivities, including anti-diabetic, anti-tumor, and inhibitory effects on T cell activation. However, it is unknown whether chrysophanol suppresses the activity of colorectal cells. In this study, we found that chrysophanol did not induce cytotoxicity in HT-29 colorectal cells. Pre-treatment with chrysophanol inhibited the mRNA levels of pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated HT-29 cells. Western blot analysis revealed that pre-treatment with chrysophanol mitigates p65 translocation and the mitogen-activated protein kinase (MAPK) pathway in activated HT-29 cells. Results from the in vivo experiment confirmed that oral administration of chrysophanol protects mice from dextran sulfate sodium (DSS)-induced IBD. Chrysophanol administration attenuates the expression of pro-inflammatory cytokines in colon tissues of the DSS-induced IBD model. In addition, we found that oral administration of chrysophanol systemically decreased the expression of effector cytokines from mesenteric lymph nodes. Therefore, these data suggest that chrysophanol has a potent modulatory effect on colorectal cells as well as exhibiting a beneficial potential for curing IBD in vivo.

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Cytokine synergy, collagenases and cartilage collagen breakdown

Biochemical Society Symposium ◽

10.1042/bss0700125 ◽

2003 ◽

Vol 70 ◽

pp. 125-133 ◽

Cited By ~ 7

Author(s):

Tim E. Cawston ◽

Jenny M. Milner ◽

Jon B. Catterall ◽

Andrew D. Rowan

Keyword(s):

Matrix Metalloproteinases ◽

Inflammatory Cytokines ◽

Activator Protein 1 ◽

Activator Protein ◽

And Cartilage ◽

Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

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