Role of cytokines in caerulein-induced acute pancreatilis of IL-1, IL-6 and TNF-α knockoul mice

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

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Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666201217163207 ◽

2020 ◽

Vol 18 ◽

Author(s):

Parimalanandhini Duraisamy ◽

Sangeetha Ravi ◽

Mahalakshmi Krishnan ◽

Catherene M. Livya ◽

Beulaja Manikandan ◽

...

Keyword(s):

Foam Cell ◽

Cell Formation ◽

Atherosclerotic Lesion ◽

Foam Cell Formation ◽

Atherosclerosis Progression ◽

Proinflammatory Mediators ◽

M1 Macrophage ◽

Tnf Α ◽

Inflammatory Site

: Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

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Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200917112802 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sridhar Muthusami ◽

Ilangovan Ramachandran ◽

Sneha Krishnamoorthy ◽

Yuvaraj Sambandam ◽

Satish Ramalingam ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Mechanisms ◽

Colorectal Carcinogenesis ◽

Model Systems ◽

Necrosis Factor Alpha ◽

Multi Stage ◽

Mechanistic Approach ◽

Tnf Α ◽

Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

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Role of inflammation in the development of colorectal cancer

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200909092908 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sridhar Muthusami ◽

R. Ileng Kumaran ◽

Kokelavani Nampalli Babu ◽

Sneha Krishnamoorthy ◽

Akash Guruswamy ◽

...

Keyword(s):

Colorectal Cancer ◽

Chronic Inflammation ◽

Interleukin 1 ◽

Cell Types ◽

Model Systems ◽

Cytokine Gene Expression ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

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Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice

Current Molecular Pharmacology ◽

10.2174/1874467212666190620143303 ◽

2019 ◽

Vol 12 (4) ◽

pp. 311-323 ◽

Cited By ~ 3

Author(s):

Salvatore Benvenga ◽

Antonio Micali ◽

Giovanni Pallio ◽

Roberto Vita ◽

Consuelo Malta ◽

...

Keyword(s):

Structural Changes ◽

Natural Antioxidants ◽

Minor Role ◽

Positive Role ◽

Testosterone Levels ◽

Tnf Α ◽

Testicular Lesions ◽

A Minor ◽

Immunohistochemical Analyses

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

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Ursodeoxycholic acid abrogates gentamicin-induced hepatotoxicity in rats: Role of NF-κB-p65/TNF-α, Bax/Bcl-xl/Caspase-3, and eNOS/iNOS pathways

Life Sciences ◽

10.1016/j.lfs.2020.117760 ◽

2020 ◽

Vol 254 ◽

pp. 117760 ◽

Cited By ~ 2

Author(s):

Fares E.M. Ali ◽

Emad H.M. Hassanein ◽

Adel G. Bakr ◽

Ehab A.M. El-Shoura ◽

Dalia A. El-Gamal ◽

...

Keyword(s):

Ursodeoxycholic Acid ◽

Caspase 3 ◽

Tnf Α

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Differential expression and role of p21cip/waf1 and p27kip1 in TNF-α-induced inhibition of proliferation in human glioma cells

Molecular Cancer ◽

10.1186/1476-4598-6-42 ◽

2007 ◽

Vol 6 (1) ◽

pp. 42 ◽

Cited By ~ 17

Author(s):

Pabbisetty Kumar ◽

Anjali Shiras ◽

Gowry Das ◽

Jayashree C Jagtap ◽

Vandna Prasad ◽

...

Keyword(s):

Differential Expression ◽

Glioma Cells ◽

Human Glioma ◽

Human Glioma Cells ◽

Inhibition Of Proliferation ◽

Tnf Α

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THE EVALUATION OF SERUM SEROTONIN LEVEL AMONG PATIENTS WITH CROHN’S DISEASE AND ITS IMPACT ON QUALITY OF LIFE

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.131 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S55-S55

Author(s):

Marcin Sochal ◽

Piotr Bialasiewicz ◽

Agata Gabryelska ◽

Renata Talar-Wojnarowska ◽

Jakub Fichna ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Sleep Quality ◽

Sleep Fragmentation ◽

Clinical Severity ◽

Serotonin Level ◽

Intestinal Physiology ◽

Tnf Α

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.

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Chandipura virus dysregulates the expression of hsa-miR-21-5p to activate NF-κB in human microglial cells

Journal of Biomedical Science ◽

10.1186/s12929-021-00748-0 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Neha Pandey ◽

Meghana Rastogi ◽

Sunit K. Singh

Keyword(s):

Expression Pattern ◽

Case Fatality ◽

Microglial Cells ◽

Luciferase Assay ◽

Western India ◽

Cellular Mirnas ◽

Over Expression ◽

Chandipura Virus ◽

Tnf Α

Abstract Background Chandipura virus (CHPV) is a negative single-stranded RNA virus of the Rhabdoviridae family. CHPV infection has been reported in Central and Western India. CHPV causes acute encephalitis with a case fatality rate of 70 % and mostly affects children below 15 years of age. CHPV infection in brain leads to neuronal apoptosis and activation of the microglial cells. The microRNAs (miRNAs) are small endogenous non-coding RNA that regulate the gene expression. Viral infections perturb the expression pattern of cellular miRNAs, which may in turn affect the expression pattern of downstream genes. This study aims to investigate hsa-miR-21-5p mediated regulation of PTEN, AKT, NF-ĸBp65, IL-6, TNF-α, and IL-1β, in human microglial cells during CHPV infection. Methods To understand the role of hsa-miR-21-5p in CHPV infection, the human microglial cells were infected with CHPV (MOI-0.1). Real-time PCR, western blotting, Luciferase assay, over-expression and knockdown techniques were used to understand the role of hsa-miR-21-5p in the regulation of PTEN, AKT and, NF-ĸBp65, IL-6, TNF-α, and IL-1β in this study. Results The hsa-miR-21-5p was found to be upregulated during CHPV infection in human microglial cells. This led to the downregulation of PTEN which promoted the phosphorylation of AKT and NF-ĸBp65. Over-expression of hsa-miR-21-5p led to the decreased expression of PTEN and promoted further phosphorylation of AKT and NF-ĸBp65 in human microglial cells. However, the inhibition of hsa-miR-21-5p using hsa-miR-21-5p inhibitor restored the expression. Conclusions This study supports the role of hsa-miR-21-5p in the regulation of pro-inflammatory genes in CHPV infected human microglial cells.

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