scholarly journals Opposing Roles of Dendritic Cell Subsets in Experimental GN

2017 ◽  
Vol 29 (1) ◽  
pp. 138-154 ◽  
Author(s):  
Sebastian Brähler ◽  
Bernd H. Zinselmeyer ◽  
Saravanan Raju ◽  
Maximilian Nitschke ◽  
Hani Suleiman ◽  
...  
Keyword(s):  
Multiphoton Microscopy ◽  
Kidney Injury ◽  
Neutrophil Infiltration ◽  
Mass Cytometry ◽  
Reporter Mouse ◽  
Renal Interstitium ◽  
Dendritic Network ◽  
Before And After ◽  
Dendritic Cell Subsets

Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c+ cells forming a network throughout the renal interstitium expressed macrophage-specific markers. In contrast, DCs marked by Zbtb46-GFP or Snx22-GFP were less abundant, concentrated around blood vessels, and round in shape. We confirmed this pattern of localization using imaging mass cytometry. Motility measurements showed that resident macrophages were sessile, whereas DCs were motile before and after inflammation. Although uninflamed glomeruli rarely contained DCs, injury with nephrotoxic antibodies resulted in accumulation of ZBTB46+ cells in the periglomerular region. ZBTB46 identifies all classic DCs, which can be categorized into two functional subsets that express either CD103 or CD11b. Depletion of ZBTB46+ cells attenuated the antibody-induced kidney injury, whereas deficiency of the CD103+ subset accelerated injury through a mechanism that involved increased neutrophil infiltration. RNA sequencing 7 days after nephrotoxic antibody injection showed that CD11b+ DCs expressed the neutrophil-attracting cytokine CXCL2, whereas CD103+ DCs expressed high levels of several anti-inflammatory genes. These results provide new insights into the distinct functions of the two major DC subsets in glomerular inflammation.

scholarly journals Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanism

2011 ◽  
Vol 300 (4) ◽  
pp. F999-F1007 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Ruth McCracken ◽  
Michael Rauchman ◽  
Monique R. Heitmeier ◽  
Ziyad Al-Aly ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Wild Type Mouse ◽  
Neutrophil Infiltration ◽  
Apical Surface ◽  
Dependent Manner ◽  
Tubular Injury ◽  
Wild Type ◽  
Direct Role

Tamm-Horsfall protein (THP) is a glycoprotein expressed exclusively in thick ascending limbs (TAL) of the kidney. We recently described a novel protective role of THP against acute kidney injury (AKI) via downregulation of inflammation in the outer medulla. Our current study investigates the mechanistic relationships among the status of THP, inflammation, and tubular injury. Using an ischemia-reperfusion model in wild-type and THP−/− mice, we demonstrate that it is the S3 proximal segments but not the THP-deficient TAL that are the main targets of tubular injury during AKI. The injured S3 segments that are surrounded by neutrophils in THP−/− mice have marked overexpression of neutrophil chemoattractant MIP-2 compared with wild-type counterparts. Neutralizing macrophage inflammatory protein-2 (MIP-2) antibody rescues S3 segments from injury, decreases neutrophil infiltration, and improves kidney function in THP−/− mice. Furthermore, using immunofluorescence volumetric imaging of wild-type mouse kidneys, we show that ischemia alters the intracellular translocation of THP in the TAL cells by partially shifting it from its default apical surface domain to the basolateral domain, the latter being contiguous to the basolateral surface of S3 segments. Concomitant with this is the upregulation, in the basolateral surface of S3 segments, of the scavenger receptor SRB-1, a putative receptor for THP. We conclude that TAL affects the susceptibility of S3 segments to injury at least in part by regulating MIP-2 expression in a THP-dependent manner. Our findings raise the interesting possibility of a direct role of basolaterally released THP on regulating inflammation in S3 segments.

scholarly journals Pharmacological Inhibition of CCR2 Signaling Exacerbates Exercise-Induced Inflammation Independently of Neutrophil Infiltration and Oxidative Stress

Immuno ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 26-39
Author(s):  
Takaki Tominaga ◽  
Jiapeng Huang ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Research Question ◽  
Neutrophil Infiltration ◽  
Humoral Factors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Pharmacological Inhibition ◽  
Before And After ◽  
Exercise Induced ◽  
And Oxidative Stress

Although exercise-induced humoral factors known as exerkines benefit systemic health, the role of most exerkines has not been investigated. Monocyte chemoattractant protein-1 (MCP-1) is a representative chemokine whose circulating concentrations increase after exercise, and it is one of the exerkines. MCP-1 is a ligand for CC chemokine receptor 2 (CCR2), which is expressed on monocytes, macrophages, and muscle cells. However, there is no information on the role of CCR2 signaling in exercise. Therefore, to investigate the research question, we administrated CCR2 antagonist or PBS to mice to inhibit CCR2 signaling before and after exercise. Our results showed that CCR2 signaling inhibition promoted exercise-induced macrophage infiltration and inflammation 24 h after exercise in muscle. CCR2 signaling inhibition also exacerbated exercise-induced inflammation immediately after exercise in muscle. However, neutrophil infiltration and oxidative stress had no contribution to exercise-induced inflammation by CCR2 signaling inhibition. CCR2 signaling inhibition also exacerbated exercise-induced inflammation immediately after exercise in kidney, liver, and adipose tissues. To summarize, pharmacological inhibition of CCR2 signaling exacerbated exercise-induced inflammation independently of neutrophil infiltration and oxidative stress.

scholarly journals Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice

2012 ◽  
Vol 303 (6) ◽  
pp. F864-F872 ◽  
Author(s):  
Nilesh Ahuja ◽  
Ana Andres-Hernando ◽  
Christopher Altmann ◽  
Rhea Bhargava ◽  
Jasna Bacalja ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Kidney Injury ◽  
Lung Injury ◽  
Prolonged Mechanical Ventilation ◽  
Kidney Injury ◽  
Neutrophil Infiltration ◽  
Bilateral Nephrectomy ◽  
Poor Outcomes ◽  
Deficient Mice

Serum IL-6 is increased in patients with acute kidney injury (AKI) and is associated with prolonged mechanical ventilation and increased mortality. Inhibition of IL-6 in mice with AKI reduces lung injury associated with a reduction in the chemokine CXCL1 and lung neutrophils. Whether circulating IL-6 or locally produced lung IL-6 mediates lung injury after AKI is unknown. We hypothesized that circulating IL-6 mediates lung injury after AKI by increasing lung endothelial CXCL1 production and subsequent neutrophil infiltration. To test the role of circulating IL-6 in AKI-mediated lung injury, recombinant murine IL-6 was administered to IL-6-deficient mice. To test the role of CXCL1 in AKI-mediated lung injury, CXCL1 was inhibited by use of CXCR2-deficient mice and anti-CXCL1 antibodies in mice with ischemic AKI or bilateral nephrectomy. Injection of recombinant IL-6 to IL-6-deficient mice with AKI increased lung CXCL1 and lung neutrophils. Lung endothelial CXCL1 was increased after AKI. CXCR2-deficient and CXCL1 antibody-treated mice with ischemic AKI or bilateral nephrectomy had reduced lung neutrophil content. In summary, we demonstrate for the first time that circulating IL-6 is a mediator of lung inflammation and injury after AKI. Since serum IL-6 is increased in patients with either AKI or acute lung injury and predicts prolonged mechanical ventilation and increased mortality in both conditions, our data suggest that serum IL-6 is not simply a biomarker of poor outcomes but a pathogenic mediator of lung injury.

scholarly journals Myostatin deficiency not only prevents muscle wasting but also improves survival in septic mice.

2020 ◽  
Author(s):  
Masayuki Kobayashi ◽  
Shingo Kasamatsu ◽  
Shohei Shinozaki ◽  
Shingo Yasuhara ◽  
Masao Kaneki
Keyword(s):  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Plasma Concentrations ◽  
Kidney Injury ◽  
Major Complication ◽  
Neutrophil Infiltration ◽  
Myeloperoxidase Activity ◽  
Bacterial Clearance ◽  
Liver And Kidney

Sepsis remains a leading cause of mortality in critically ill patients. Muscle wasting is a major complication of sepsis and negatively affects clinical outcomes. Despite intense investigation for many years, the molecular mechanisms underlying sepsis-related muscle wasting are not fully understood. In addition, a potential role of muscle wasting in disease development of sepsis has not been studied. Myostatin is a myokine that downregulates skeletal muscle mass. We studied the effects of myostatin deficiency on muscle wasting and other clinically relevant outcomes, including mortality and bacterial clearance, in mice. Myostatin deficiency prevented muscle atrophy along with inhibition of increases in MuRF-1 and atrogin-1 expression and phosphorylation of STAT3 (major players of muscle wasting) in septic mice. Moreover, myostatin deficiency improved survival and bacterial clearance of septic mice. Sepsis-induced liver dysfunction, acute kidney injury and neutrophil infiltration into the liver and kidney were consistently mitigated by myostatin deficiency, as indicated by plasma concentrations of AST, ALT and NGAL and myeloperoxidase activity in the organs. Myostatin deficiency also inhibited sepsis-induced increases in plasma HMGB1 and MIC-1/GDF-15 concentrations. These results indicate that myostatin plays an important role not only in muscle wasting but also in other clinically relevant outcomes in septic mice. Furthermore, our data raise the possibility that muscle wasting may not be simply a complication, but myostatin-mediated muscle cachexia and related changes in muscle may actually drive the development of sepsis as well.

Child and Adolescent Suicides in Bosnia and Herzegovina Before and After the War (1992–1995)

Crisis ◽  
2010 ◽  
Vol 31 (3) ◽  
pp. 160-164 ◽  
Author(s):  
Almir Fajkic ◽  
Orhan Lepara ◽  
Martin Voracek ◽  
Nestor D. Kapusta ◽  
Thomas Niederkrotenthaler ◽  
...  
Keyword(s):  
Bosnia And Herzegovina ◽  
Age Differences ◽  
Suicide Risk ◽  
Child And Adolescent ◽  
Youth Suicide ◽  
Southeastern Europe ◽  
Suicide Rates ◽  
Before And After ◽  
Sex And Age Differences

Background: Evidence on youth suicides from Southeastern Europe is scarce. We are not aware of previous reports from Bosnia and Herzegovina, which experienced war from 1992 to 1995. Durkheim’s theory of suicide predicts decreased suicide rates in wartime and increased rates afterward. Aims: To compare child and adolescent suicides in Bosnia and Herzegovina before and after the war. Methods: Data on youth suicide for prewar (1986–90) and postwar (2002–06) periods were analyzed with respect to prevalence, sex and age differences, and suicide methods. Suicide data from 1991 through 2001 were not available. Results: Overall youth suicide rates were one-third lower in the postwar than in the prewar period. This effect was most pronounced for girls, whose postwar suicide rates almost halved, and for 15–19-year-old boys, whose rates decreased by about a one-fourth. Suicides increased among boys aged 14 or younger. Firearm suicides almost doubled proportionally and were the predominant postwar method, while the most common prewar method had been hanging. Conclusions: The findings from this study indicate the need for public education in Bosnia and Herzegovina on the role of firearm accessibility in youth suicide and for instructions on safe storage in households. Moreover, raising societal awareness about suicide risk factors and suicide prevention is needed.

Strategic Role of Zakat in Multidimensional Quality of Life in Sijunjung, Indonesia

2018 ◽  
Vol 15 (1) ◽  
pp. 55-72
Author(s):  
Herlin Hamimi ◽  
Abdul Ghafar Ismail ◽  
Muhammad Hasbi Zaenal
Keyword(s):  
Quality Of Life ◽  
Positive Impact ◽  
Wealth Distribution ◽  
Absolute Poverty ◽  
Before And After ◽  
The Status ◽  
Being There ◽  
The Impact

Zakat is one of the five pillars of Islam which has a function of faith, social and economic functions. Muslims who can pay zakat are required to give at least 2.5 per cent of their wealth. The problem of poverty prevalent in disadvantaged regions because of the difficulty of access to information and communication led to a gap that is so high in wealth and resources. The instrument of zakat provides a paradigm in the achievement of equitable wealth distribution and healthy circulation. Zakat potentially offers a better life and improves the quality of human being. There is a human quality improvement not only in economic terms but also in spiritual terms such as improving religiousity. This study aims to examine the role of zakat to alleviate humanitarian issues in disadvantaged regions such as Sijunjung, one of zakat beneficiaries and impoverished areas in Indonesia. The researcher attempted a Cibest method to capture the impact of zakat beneficiaries before and after becoming a member of Zakat Community Development (ZCD) Program in material and spiritual value. The overall analysis shows that zakat has a positive impact on disadvantaged regions development and enhance the quality of life of the community. There is an improvement in the average of mustahik household incomes after becoming a member of ZCD Program. Cibest model demonstrates that material, spiritual, and absolute poverty index decreased by 10, 5, and 6 per cent. Meanwhile, the welfare index is increased by 21 per cent. These findings have significant implications for developing the quality of life in disadvantaged regions in Sijunjung. Therefore, zakat is one of the instruments to change the status of disadvantaged areas to be equivalent to other areas.

SUBLINGUAL VITAMIN D3 DRUG THERAPY IN VITAMIN D DEFICIENCY PATIENTS AT PRAVARA RURAL HOSPITAL

2019 ◽  
pp. 18-20
Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Serum Vitamin ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
Significant Difference ◽  
Before And After

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route

Arthroscopy in Arthrosis: Is It Worth it? A case Presentation

2018 ◽  
Vol 69 (8) ◽  
pp. 2232-2235
Author(s):  
Marius Moga ◽  
Mark Edward Pogarasteanu ◽  
Antoine Edu
Keyword(s):  
Clinical Status ◽  
Loose Body ◽  
Point Of View ◽  
The Other ◽  
Joint Range Of Motion ◽  
Objective Evidence ◽  
Before And After ◽  
Total Knee ◽  
Joint Range

The role of arthroscopy in incipient and mild arthrosis, even combined with proximal tibial ostetomy, is well known and well documented. On the other hand, its role in the treatment of advanced arthrosis of the large joints, especially the knee, is a subject of controversy. The proponents of the use of arthroscopy in advanced arthrosis claim that meniscectomy, synovectomy, ostophytectomy, chondral lesion stabilization, arthroscopic release, plica and loose body removal greatly improve the quality of life for most patients, especially if followed by the use of viscoelastic injection, by diminishing pain and improving joint range of motion. The opponents claim that, even though the advantages are clear in the cases that refuse arthroplasty, in all the other cases the surgical indication should be total knee arthroplasty, as the clinical relief is temporary, but with all the risks of a surgical intervention. We have conducted an overview of the recent literature, in order to find objective evidence to sustain either point of view. We focused on articles published that included an objective measurement of before and after clinical status through clinical scores and objective measurements. We also focused on the follow-up period and on the evolution of the pathology after arthroscopy.

Sign in / Sign up

Export Citation Format

Share Document