P0912AKIDNEY AGING CONSTITUTES INFLAMMATORY PROCESS THAT CONTRIBUTES TO EXACERBATION OF KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Su Woong Jung ◽  
Ju-Young Moon ◽  
Yang-Gyun Kim ◽  
Kyung Hwan Jeong ◽  
Sang-Ho Lee
Keyword(s):  
Inflammatory Response ◽  
Renal Damage ◽  
Middle Age ◽  
Kidney Injury ◽  
Adaptive Immune System ◽  
Transcriptional Level ◽  
Transcript Profile ◽  
Adaptive Immune ◽  
Age Related ◽  
Old Mice

Abstract Background and Aims Aging is a natural process accompanied by decline of regenerative potential. Some argue that aging process is just an irreversible physiologic process, whereas some advocate that it should be viewed as disease. Method To determine the nature of kidney aging and kidney disease at transcriptional level, whole kidney RNA sequencing was performed on young (2-month-old), middle-aged (12-month-old), and old (24-month-old) mice and young mice with adenine-induced nephropathy. In addition, young and old mice were fed with either standard or adenine-enriched diet for 4 weeks, and then the degree of renal injury was compared. Results The transcript profile of the old kidneys was mostly involved in inflammation and activation of innate and adaptive immune system and almost same to the transcript alterations of adenine-induced nephropathy. The genes implicated in fibrosis were downregulated until middle-age period, and then upregulated with the advance of age. The old kidneys showed augmented inflammatory response in a model of adenine-induced nephropathy compared with young kidneys, leading to more widespread fibrosis. Conclusion These findings showed that the pathophysiologic process of kidney aging and adenine-induced kidney injury shows similar natures in the context of inflammation and immune response. When kidney injury is superimposed on the aged kidneys, age-related inflammation potentiates inflammatory response and results in increased renal damage.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2020 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Specific Igg ◽  
Ifn Γ ◽  
Old Mice

Abstract Backgroud: As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between children and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown.Methods: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA.Results: Our results found that childhood mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group.Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2019 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Cd4 T Cells ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Ifn Γ ◽  
Old Mice

Abstract Background As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between childhood and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown. Methods 4 and 8-week-old mice were used to mimic childhood and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-special IgG were measured by ELISA. Results Infant mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4 + T-bet + IFN-γ + Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4 + GATA3 + IL-4 + Th2 cells and CD4 + CXCR5 + Tfh cells, and IL-4 production in the 8-week-old mice obviously increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-special IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4 + or activated CD4 + T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusion We consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4 + T cells exhaustion.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2020 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Specific Igg ◽  
Ifn Γ ◽  
Old Mice

Abstract Backgroud: As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between childhood and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown. Methods: 4 and 8-week-old mice were used to mimic childhood and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. Results: Our results found that childhood mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

scholarly journals Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

2020 ◽  
Author(s):  
Qiu-bo Wang ◽  
Yun-ting Du ◽  
Fei Liu ◽  
Xiao-dan Sun ◽  
Xun Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Survival Rate ◽  
Plasmodium Yoelii ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Adaptive Immune ◽  
Age Related ◽  
Specific Igg ◽  
Ifn Γ ◽  
Old Mice

Abstract Backgroud: As the quest to eradicate malaria continues, it is important to clarify the opposite clinical outcomes between children and adulthood. The relationship between adaptive immune response and age-related malaria infection remains unknown. Methods: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA. Results: Our results found that childhood mice were more susceptible to P. yoelii 17XNL infection, with lower survival rate and higher parasitemia. The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4+T-bet+IFN-γ+ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4+GATA3+IL-4+ Th2 cells and CD4+CXCR5+ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4+ or activated CD4+ T cells in the 8-week-old mice as compared to the 4-week-old group. Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4+ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.

scholarly journals Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Marquez-Exposito ◽  
Lucia Tejedor-Santamaria ◽  
Laura Santos-Sanchez ◽  
Floris A. Valentijn ◽  
Elena Cantero-Navarro ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Cellular Senescence ◽  
Immune Cells ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Nuclear Staining ◽  
Age Related ◽  
Regulated Necrosis ◽  
Old Mice

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (Il-6, Tgfb1, Ctgf, and Serpine1). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells (“immunosenescence”) are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells.

Novel Mechanisms for Resolution of Liver Inflammation: Therapeutic Implications

2021 ◽  
Author(s):  
Benedikt Kaufmann ◽  
Agustina Reca ◽  
Andrea D. Kim ◽  
Ariel E. Feldstein
Keyword(s):  
Inflammatory Response ◽  
Adaptive Immune System ◽  
Hepatic Function ◽  
New Paradigm ◽  
Therapeutic Implications ◽  
Adaptive Immune ◽  
Disease States ◽  
Insight Into ◽  
Stimulation Of

AbstractTraditional concepts have classically viewed resolution of inflammation as a passive process yet insight into the pathways by which inflammation is resolved has challenged this idea. Resolution has been revealed as a highly dynamic and active event that is essential to counteract the dysregulated inflammatory response that drives diverse disease states. Abrogation of the hepatic inflammatory response through the stimulation of proresolving mechanisms represents a new paradigm in the setting of chronic inflammatory-driven liver diseases. Elucidation of the role of different cells of the innate and adaptive immune system has highlighted the interplay between them as an important orchestrator of liver repair. A finely tuned interaction between neutrophils and macrophages has risen as revolutionary mechanism that drives the restoration of hepatic function and architecture. Specialized proresolving mediators have also been shown to act as stop signals of the inflammatory response and promote resolution as well as tissue regeneration. In this review, we discuss the discovery and understanding of the mechanisms by which inflammation is resolved and highlight novel proresolving pathways that represent promising therapeutic strategies.

scholarly journals Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives

2018 ◽  
Vol 19 (12) ◽  
pp. 3701 ◽  
Author(s):  
Rita Del Pinto ◽  
Claudio Ferri
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Common Denominator ◽  
Low Grade ◽  
Dna Targeting ◽  
Adaptive Immune ◽  
Immune System Dysfunction ◽  
Age Related ◽  
Genetic Modifications ◽  
Low Grade Inflammation

Low-grade chronic inflammation is a common denominator in atherogenesis and related diseases. Solid evidence supports the occurrence of an impairment in the innate and adaptive immune system with senescence, favoring the development of acute and chronic age-related diseases. Cardiovascular (CV) diseases (CVD), in particular, are a leading cause of death even at older ages. Inflammation-associated mechanisms that contribute to CVD development include dysregulated redox and metabolic pathways, genetic modifications, and infections/dysbiosis. In this review, we will recapitulate the determinants and consequences of the immune system dysfunction at older age, with particular focus on the CV system. We will examine the currently available and potential future strategies to counteract accelerated CV aging, i.e., nutraceuticals, probiotics, caloric restriction, physical activity, smoking and alcohol cessation, control of low-grade inflammation sources, senolytic and senescence-modulating drugs, and DNA-targeting drugs.

scholarly journals Moderate aging does not exacerbate cisplatin-induced kidney injury or fibrosis despite altered inflammatory cytokine expression and immune cell infiltration

2019 ◽  
Vol 316 (1) ◽  
pp. F162-F172 ◽  
Author(s):  
Cierra N. Sharp ◽  
Mark Doll ◽  
Tess V. Dupre ◽  
Levi J. Beverly ◽  
Leah J. Siskind
Keyword(s):  
Acute Kidney Injury ◽  
Risk Factor ◽  
Inflammatory Response ◽  
Immune Cell ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Cell Infiltration ◽  
High Dose ◽  
Immune Cell Infiltration ◽  
Old Mice

Aging is a risk factor for certain forms of kidney injury due to normal physiological changes, but the role of aging in cisplatin-induced kidney injury is not well defined in humans or animal models of the disease. To improve on current knowledge in this field, we treated 8- and 40-wk-old FVB/n mice with one high dose of cisplatin as a model of acute kidney injury or with repeated low doses of cisplatin (7 mg/kg cisplatin once a week for 4 wk) as a clinically relevant model of chronic kidney disease to determine if aging exacerbates cisplatin-induced kidney injury. Levels of acute kidney injury were comparable in 8- and 40-wk-old mice. In 40-wk-old mice, fibrotic markers were elevated basally, but treatment with cisplatin did not exacerbate fibrosis. We concluded that this may be the result of a decreased inflammatory response in 40-wk-old cisplatin-treated mice compared with 8-wk-old mice. Despite a decreased inflammatory response, the level of immune cell infiltration was greater in 40-wk-old cisplatin-treated mice than 8-wk-old mice. Our data highlight the importance of examining age as a risk factor for cisplatin-induced kidney injury.

scholarly journals Effects of Zinc Status and Aging on Age-Related Immune Dysfunction and Chronic Inflammation

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1854-1854
Author(s):  
Carmen Wong ◽  
Kendra Braun ◽  
John Bouranis ◽  
Edward Davis ◽  
Thomas Sharpton ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Zinc Deficiency ◽  
Serum Zinc ◽  
Immune Dysfunction ◽  
Zinc Status ◽  
Aged Mice ◽  
Age Related ◽  
Marginal Zinc Deficiency ◽  
Old Mice

Abstract Objectives Aging is associated with progressive immune dysfunction, including impaired adaptive response, increased susceptibility to infection, and reduced vaccination efficacy. Aging is also associated with chronic inflammation that correlated with the promotion of many age-related diseases. Zinc is an essential micronutrient critical for immune function. In US, 12% of the population do not consume the estimated average requirement for zinc. The prevalence of inadequate zinc intake is even higher among older populations, and are at increased risk for marginal zinc deficiency. Effects of zinc deficiency share similarities to age-related immune dysfunction, including impaired adaptive immunity and increased in proinflammatory response. The goal of this study is to understand the effects of zinc status and aging on age-related immune dysfunction and chronic inflammation. We hypothesize that age-related decline in zinc status contributes to immune dysregulation and chronic inflammation in the elderly. Methods We studied the effects of dietary zinc supplementation and marginal zinc deficiency on changes in mucosal immunity and inflammatory response in young and old mice. Young (2 mo) and old (24 mo) C57Bl/6 mice were fed a zinc adequate (ZA, 30 ppm Zn), zinc supplemented (ZS, 300 ppm Zn), or marginal zinc deficient (MZD, 6 ppm Zn) diets for 6 wks. Serum zinc status, cytokines, and naïve/memory T-cell phenotypes, were determined at the end of the study. Results Old mice had reduced zinc and increased proinflammatory cytokines MCP1 and IL6 in the serum, increased Th1/Th17/inflammatory cytokines (IFNγ, IL17, TNFα, respectively) and decreased naïve CD4 T-cells in the mesenteric lymph nodes (MLN). ZS significantly increased serum zinc levels, decreased TNFα, IFNγ, IL17 in MLN, and increased naïve T-cell populations in aged mice. MZD further reduced serum zinc and increased serum IL6 levels in aged mice. Conclusions ZS improved the immune function of aged mice and reduced inflammatory response, and MZD further increased age-related inflammation. Our data suggest that zinc status is an important contributing factor in age-related immune dysfunction and chronic inflammation. Funding Sources NIFA, USDA.

Defences against infection

2018 ◽  
Author(s):  
Ajit Lalvani ◽  
Katrina Pollock
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
The Body ◽  
Innate Immune ◽  
Acute Inflammatory Response ◽  
Adaptive Immune ◽  
Immune Deficiencies ◽  
Prolonged Response

The immune system is classified into a series of component parts, each specialized to defend the host against infection. Cells of the innate immune system are distributed throughout the body, in the tissues, and in the circulation, to defend against the first signs of danger, combining the acute inflammatory response with the ability to kill and remove invading pathogens. Monocytes, macrophages, and neutrophils phagocytose and kill exogenous and endogenous targets, using both oxygen-dependent and oxygen-independent mechanisms. The adaptive immune system creates a structurally specific and prolonged response, mediated by lymphocytes to clear infection and generate immunological memory. In this chapter, the functions of the innate and adaptive immune system are reviewed, together with the clinical features and investigation of acquired and inherited immune deficiencies.

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