Doxorubicin Paradoxically Ameliorates Tumor-Induced Inflammation in Young Mice

Doxorubicin (DOX) is one of the most widely used chemo-therapeutic agents in pediatric oncology. DOX elicits an inflammatory response in multiple organs, which contributes to DOX-induced adverse effects. Cancer itself causes inflammation leading to multiple pathologic conditions. The current study investigated the inflammatory response to DOX and tumors using an EL4-lymphoma, immunocompetent, juvenile mouse model. Four-week old male C57BL/6N mice were injected subcutaneously with EL4 lymphoma cells (5 × 104 cells/mouse) in the flank region, while tumor-free mice were injected with vehicle. Three days following tumor implantation, both tumor-free and tumor-bearing mice were injected intraperitoneally with either DOX (4 mg/kg/week) or saline for 3 weeks. One week after the last DOX injection, the mice were euthanized and the hearts, livers, kidneys, and serum were harvested. Gene expression and serum concentration of inflammatory markers were quantified using real-time PCR and ELISA, respectively. DOX treatment significantly suppressed tumor growth in tumor-bearing mice and caused significant cardiac atrophy in tumor-free and tumor-bearing mice. EL4 tumors elicited a strong inflammatory response in the heart, liver, and kidney. Strikingly, DOX treatment ameliorated tumor-induced inflammation paradoxical to the effect of DOX in tumor-free mice, demonstrating a widely divergent effect of DOX treatment in tumor-free versus tumor-bearing mice.

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Redox-Modulating Agents in the Treatment of Viral Infections

International Journal of Molecular Sciences ◽

10.3390/ijms21114084 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4084 ◽

Cited By ~ 6

Author(s):

Paola Checconi ◽

Marta De Angelis ◽

Maria Elena Marcocci ◽

Alessandra Fraternale ◽

Mauro Magnani ◽

...

Keyword(s):

Inflammatory Response ◽

Redox State ◽

Viral Infections ◽

Rna Virus ◽

Influenza Virus Infection ◽

Redox Balance ◽

Physiological Conditions ◽

Cell Functions ◽

Enzymatic Systems ◽

Strong Inflammatory Response

Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.

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Mechanisms in allergic airway inflammation – lessons from studies in the mouse

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399408000707 ◽

2008 ◽

Vol 10 ◽

Cited By ~ 26

Author(s):

Bennett O.V. Shum ◽

Michael S. Rolph ◽

William A. Sewell

Keyword(s):

Inflammatory Response ◽

Airway Inflammation ◽

Cellular Response ◽

Allergic Airway Inflammation ◽

Cell Types ◽

Therapeutic Agents ◽

Chronic Inflammatory Disease ◽

Pathological Feature ◽

Cytokines And Chemokines ◽

Novel Therapeutic

Asthma is a chronic inflammatory disease of the airways, involving recurrent episodes of airway obstruction and wheezing. A common pathological feature in asthma is the presence of a characteristic allergic airway inflammatory response involving extensive leukocyte infiltration, mucus overproduction and airway hyper-reactivity. The pathogenesis of allergic airway inflammation is complex, involving multiple cell types such as T helper 2 cells, regulatory T cells, eosinophils, dendritic cells, mast cells, and parenchymal cells of the lung. The cellular response in allergic airway inflammation is controlled by a broad range of bioactive mediators, including IgE, cytokines and chemokines. The asthmatic allergic inflammatory response has been a particular focus of efforts to develop novel therapeutic agents. Animal models are widely used to investigate inflammatory mechanisms. Although these models are not perfect replicas of clinical asthma, such studies have led to the development of numerous novel therapeutic agents, of which some have already been successful in clinical trials.

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Combination of baicalein and docetaxel additively inhibits the growth of non-small cell lung cancer in vivo

Traditional Medicine and Modern Medicine ◽

10.1142/s2575900018500131 ◽

2018 ◽

Vol 01 (03) ◽

pp. 213-218 ◽

Cited By ~ 1

Author(s):

Linwei Lu ◽

Zhengxiao Zhao ◽

Lumei Liu ◽

Weiyi Gong ◽

Jingcheng Dong

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung ◽

Tumor Bearing ◽

Liver And Kidney ◽

To Receive

Objective: The objective of this study is to preliminarily evaluate the efficacy of the combination of baicalein and docetaxel on non-small cell lung cancer (NSCLC) in vivo. Methods: The subcutaneous model was established by inoculation of A549 cells, and then these tumor-bearing mice were randomly assigned to eight groups to receive normal saline (NS) as control, baicalein alone, Taxotere[Formula: see text] (docetaxel injection) alone or the combination of baicalein and Taxotere[Formula: see text]. The effect of the combination treatment was evaluated by [Formula: see text] value. Tumors were harvested for TUNEL and CD31 immunohistochemical staining and important organs for H&E staining. Results: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg significantly reduced tumor weight and inhibited the growth rate of tumor, displaying the additive effect indicated by the [Formula: see text] value. Increased apoptosis and decreased tumor angiogenesis also provided pathological evidence. Additionally, baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg did not increase toxicity in lung, liver and kidney. Conclusion: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg additively inhibits the growth of NSCLC in vivo, and the mechanism underlying remains to be discovered.

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Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis

AJP Renal Physiology ◽

10.1152/ajprenal.00138.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. F356-F362 ◽

Cited By ~ 46

Author(s):

John Kanellis ◽

Roger Bick ◽

Gabriela Garcia ◽

Luan Truong ◽

Chun Chui Tsao ◽

...

Keyword(s):

Inflammatory Response ◽

Intracellular Calcium ◽

In Vivo Studies ◽

Cellular Processes ◽

Multiple Organs ◽

Chemotactic Protein ◽

Stromal Cell Derived Factor ◽

Mammalian Counterpart

In macrophages, changes in intracellular calcium have been associated with activation of cellular processes that regulate cell adhesion and motility and are important for the response of macrophages to antigenic stimuli. The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) is expressed in multiple organs including the thymus and spleen, and hence, we hypothesized that it may have a role in modulating the immune/inflammatory response. Using murine macrophage-like (RAW264.7) and human monoblast-like (U937) cells to study chemotaxis in vitro, we found that STC1 attenuated chemokinesis and diminished the chemotactic response to monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α. Consistent with these findings, STC1 blunted the rise in intracellular calcium following MCP-1 stimulation in RAW264.7 cells. In vivo studies suggested differential expression of STC1 in obstructed kidney and localization to macrophages. MCP-1 and STC1 transcripts were both upregulated following ureteric obstruction, suggesting a functional association between the two genes. Our data suggest a role for mammalian STC1 in modulating the immune/inflammatory response.

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Investigating the Histological Changes in Heart, Lung, Liver and Kidney of Male Albino Mice Treated with Ivabradine

Baghdad Science Journal ◽

10.21123/bsj.2019.16.3(suppl.).0719 ◽

2019 ◽

Vol 16 (3(Suppl.)) ◽

pp. 0719

Author(s):

Hadeel Kamil Khaleel

Keyword(s):

Pulmonary Congestion ◽

Male Mice ◽

Histological Changes ◽

Cardiac Atrophy ◽

Vascular Congestion ◽

Myocardial Degeneration ◽

Liver And Kidney ◽

Tissue Changes ◽

Myocardial Fibers ◽

Hepatocyte Necrosis

The present study aimed to investigate the histological changes of heart, lung, liver and kidney which caused by different concentrations (10, 20 and 40 mg/kg) of Ivabradine. Results of the study revealed some histological changes represented by aggregation of the lymphocytes around respiratory bronchioles of the lung. In the liver, the drug caused hepatocyte necrosis and infiltration of the lymphocytes. In Kidney, there are no histopathological modifications in the tissue after the animals treated with 10 mg\kg of Ivabradine. When the animals treated with Ivabradine drug at 20mg/kg of bw, dose showed vascular congestion between myocardial fibers of heart. Emphysematous changes of the alveoli and infiltration of lymphocytes around respiratory bronchioles of lung. In the liver there were dilated blood sinusoids. Also, there are vascular congestion and congestion of capillaries in the glomerular of kidney. Male mice treated with Ivabradine drug at 40 mg/kg of bw cause increase spaces between myocardial fibers, cardiac atrophy and myocardial degeneration in the heart. In addition, there are infiltration of lymphocytes around respiratory bronchioles, pulmonary congestion and emphysematous changes of the alveoli in lung. In the liver, the drug cause amyloid deposition and degeneration of hepatocytes. Furthermore, the drug caused vascular congestion in the kidney. Conclusion: From the current study, we conclude that the different concentrations of Ivabradine caused tissue changes in the heart, lung, liver and kidneys. The study should continue using different drugs and concentrations.

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Mardivirus Infection and Persistence in Feathers of a Chicken Model Harboring a Local Autoimmune Response

Microorganisms ◽

10.3390/microorganisms8101613 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1613

Author(s):

Gisela F. Erf ◽

Gilles Le Pape ◽

Sylvie Rémy ◽

Caroline Denesvre

Keyword(s):

Inflammatory Response ◽

Newcastle Disease ◽

Marek's Disease ◽

Autoimmune Response ◽

Marek’S Disease ◽

Autoimmune Destruction ◽

Strong Inflammatory Response ◽

Destruction Of Melanocytes ◽

Chicken Model

Herpesvirus of turkey (HVT) is commonly used as a vaccine to protect chickens against Marek’s disease. Following vaccination, HVT infects feathers where it can be detected in all chicken lines examined. Unlike the parental Brown line (BL), Smyth line (SL) chickens develop vitiligo, due to autoimmune destruction of melanocytes in feathers. Previous reports showed a strong inflammatory response in Smyth chickens’ feathers at vitiligo onset, that subsided once melanocytes were destroyed, and depigmentation was complete. Here, we questioned whether the local autoimmune response in the Smyth model influences HVT infection and persistence in feathers. For this, one-day-old SL and BL chickens were vaccinated with Newcastle disease (rHVT-ND). Vitiligo was scored and HVT loads in pigmented and non-pigmented growing feathers were quantified regularly over 20 weeks. Chickens of both lines showed moderate HVT loads in feathers. At the onset of active vitiligo, the HVT load was significantly higher in SL compared to BL feathers. However, no difference in HVT loads was noticed between pigmented and non-pigmented feathers from SL chickens. Therefore, surprisingly, the inflammatory response in feathers of SL chickens did not inhibit HVT infection and persistence, but on the contrary, temporarily promoted HVT infection in feathers.

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Anti-Tumor Effects of the Polysaccharide Isolated from Tarphochlamys Affinis in H22 Tumor-Bearing Mice

Cellular Physiology and Biochemistry ◽

10.1159/000447811 ◽

2016 ◽

Vol 39 (3) ◽

pp. 1040-1050 ◽

Cited By ~ 11

Author(s):

Xiaojun Tang ◽

Jianchun Huang ◽

Hao Xiong ◽

Keyuan Zhang ◽

Chunxia Chen ◽

...

Keyword(s):

T Lymphocytes ◽

Tumor Cell ◽

Relative Weight ◽

Underlying Mechanism ◽

Host Immune System ◽

Protective Effects ◽

Tumor Bearing ◽

Liver And Kidney ◽

Anti Tumor Activity

Background: The previous studies have demonstrated that the polysaccharide isolated from Tarphochlamys affinis (PTA) exhibits anti-tumor effect on S180 tumor-bearing mice and protective effects against hepatic injury. Methods: In this study, we investigated the anti-tumor activity and possible underlying mechanism of PTA on liver cancer using a murine H22 hepatocarcinoma model. Results: PTA was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo. The relative weight of immune organs (spleen and thymus) and lymphocyte proliferation induced by ConA or LPS were improved after PTA treatment. Furthermore, treatment with PTA promoted immune-stimulating serum cytokine secretion in H22 tumor-bearing mice. Additionally, the percentage of CD4+ T lymphocytes, CD8+ T lymphocytes and NK cells was increased in tumor-bearing mice following PTA administration. In tumor tissue, PTA significantly up-regulated the expression of Bax and p53 proteins and down-regulated the expression of Bcl-2 protein. In addition, at the therapeutic dose, PTA displayed very few toxic effects to major organs, such as the liver and kidney, in tumor-bearing mice. Conclusion: In H22 tumor-bearing mice, PTA exhibited prominent anti-tumor activity in vivo. The possible mechanism of action might be related to enhanced host immune system function and induction of H22 tumor cell apoptosis.

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Complement Properdin Regulates the Metabolo-Inflammatory Response to a High Fat Diet

Medicina ◽

10.3390/medicina56090484 ◽

2020 ◽

Vol 56 (9) ◽

pp. 484

Author(s):

Rόisín C. Thomas ◽

Ramiar Kheder ◽

Hasanain Alaridhee ◽

Naomi Martin ◽

Cordula M. Stover

Keyword(s):

Inflammatory Response ◽

Complement Activation ◽

High Fat Diet ◽

Ultrastructural Changes ◽

Dominant Factor ◽

High Fat ◽

Circulating Microparticles ◽

Fatty Acid Transporter ◽

Liver And Kidney ◽

Obesity In Mice

Background and objectives: Overnutrition leads to a metabolic and inflammatory response that includes the activation of Complement. Properdin is the only amplifier of complement activation and increases the provision of complement activation products. Its absence has previously been shown to lead to increased obesity in mice on a high fat diet. The aim of this study was to determine ways in which properdin contributes to a less pronounced obese phenotype. Materials and Methods: Wild type (WT) and properdin deficient mice (KO) were fed a high-fat diet (HFD) for up to 12 weeks. Results: There was a significant increase in liver triglyceride content in the KO HFD group compared to WT on HFD. WT developed steatosis. KO had an additional inflammatory component (steatohepatitis). Analysis of AKT signalling by phosphorylation array supported a decrease in insulin sensitivity which was greater for KO than WT in liver and kidney. There was a significant decrease of C5L2 in the fat membranes of the KO HFD group compared to the WT HFD group. Circulating microparticles in KO HFD group showed lower presence of C5L2. Expression of the fatty acid transporter CD36 in adipose tissue was increased in KO on HFD and was also significantly increased in plasma of KO HFD mice compared to WT on HFD. CD36 was elevated on microparticles from KO on HFD. Ultrastructural changes consistent with obesity-associated glomerulopathy were observed for both HFD fed genotypes, but tubular strain was greater in KO. Conclusion: Our work demonstrates that complement properdin is a dominant factor in limiting the severity of obesity-associated conditions that impact on liver and kidney. The two receptors, C5L2 and CD36, are downstream of the activity exerted by properdin.

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Role of Adrenomedullin in Lyme Disease

Infection and Immunity ◽

10.1128/iai.00630-10 ◽

2010 ◽

Vol 78 (12) ◽

pp. 5307-5313 ◽

Cited By ~ 2

Author(s):

Meghan L. Marre ◽

Courtney T. Darcy ◽

Janeth Yinh ◽

Shizuo Akira ◽

Satoshi Uematsu ◽

...

Keyword(s):

Inflammatory Response ◽

Inflammatory Responses ◽

Lyme Arthritis ◽

Signaling Cascades ◽

Mammalian Host ◽

Phosphatidylinositol 3 Kinase ◽

Raw264.7 Macrophages ◽

Osteoarthritis Patient ◽

Strong Inflammatory Response

ABSTRACT Borrelia burgdorferi stimulates a strong inflammatory response during infection of a mammalian host. To understand the mechanisms of immune regulation employed by the host to control this inflammatory response, we focused our studies on adrenomedullin, a peptide produced in response to bacterial stimuli that exhibits antimicrobial activity and regulates inflammatory responses by modulating the expression of inflammatory cytokines. Specifically, we investigated the effect of B. burgdorferi on the expression of adrenomedullin as well as the ability of adrenomedullin to dampen host inflammatory responses to the spirochete. The concentration of adrenomedullin in the synovial fluid of untreated Lyme arthritis patients was elevated compared with that in control osteoarthritis patient samples. In addition, coculture with B. burgdorferi significantly increased the expression of adrenomedullin in RAW264.7 macrophages through MyD88-, phosphatidylinositol 3-kinase (PI3-K)-, and p38-dependent signaling cascades. Furthermore, the addition of exogenous adrenomedullin to B. burgdorferi-stimulated RAW264.7 macrophages resulted in a significant decrease in the induction of proinflammatory cytokines. Taken together, these results suggest that B. burgdorferi increases the production of adrenomedullin, which in turn negatively regulates the B. burgdorferi-stimulated inflammatory response.

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