The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is “Inflammation” Always Inflammation?

Kulkarni, Onkar P.; Lichtnekert, Julia; Anders, Hans‐Joachim; Mulay, Shrikant R.

doi:10.1155/2016/2856213

Cited by 69 publications

(54 citation statements)

References 135 publications

(134 reference statements)

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“…Their heterogeneity is determined by the microenvironment. [20][21][22][23][24] We, therefore, employed flow cytometry to understand the diversity of phenotypes among the infiltrating macrophages. We noted that nephrocalcinosis is associated with increased numbers of cluster of differentiation (CD)45þ leukocytes in oxalate-treated mice, compared with the control group (Figure 3b).…”

Section: Nlrp3 Inhibition Induces a Shift In Nephrocalcinosis-relatedmentioning

confidence: 99%

The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury

Anders

Suárez-Álvarez

Grigorescu

et al. 2018

Kidney International

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Primary/secondary hyperoxalurias involve nephrocalcinosis-related chronic kidney disease (CKD) leading to end-stage kidney disease. Mechanistically, intrarenal calcium oxalate crystal deposition is thought to elicit inflammation, tubular injury and atrophy, involving the NLRP3 inflammasome. Here, we found that mice deficient in NLRP3 and ASC adaptor protein failed to develop nephrocalcinosis, compromising conclusions on nephrocalcinosis-related CKD. In contrast, hyperoxaluric wild-type mice developed profound nephrocalcinosis. NLRP3 inhibition using the β-hydroxybutyrate precursor 1,3-butanediol protected such mice from nephrocalcinosis-related CKD. Interestingly, the IL-1 inhibitor anakinra had no such effect, suggesting IL-1-independent functions of NLRP3. NLRP3 inhibition using 1,3-butanediol treatment induced a shift of infiltrating renal macrophages from pro-inflammatory (CD45F4/80CD11bCX3CR1CD206) and pro-fibrotic (CD45F4/80CD11bCX3CR1CD206TGFβ) to an anti-inflammatory (CD45F4/80CD11bCD206TGFβ) phenotype, and prevented renal fibrosis. Finally, in vitro studies with primary murine fibroblasts confirmed the non-redundant role of NLRP3 in the TGF-β signaling pathway for fibroblast activation and proliferation independent of the NLRP3 inflammasome complex formation. Thus, nephrocalcinosis-related CKD involves NLRP3 but not necessarily via intrarenal IL-1 release but rather via other biological functions including TGFR signaling and macrophage polarization. Hence, NLRP3 may be a promising therapeutic target in hyperoxaluria and nephrocalcinosis.

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Section: Nlrp3 Inhibition Induces a Shift In Nephrocalcinosis-relatedmentioning

confidence: 99%

The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury

Anders

Suárez-Álvarez

Grigorescu

et al. 2018

Kidney International

Self Cite

175

129

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“…Their failure results in illness. The human immune system modulates many important biological protective processes [10][11][12]. It coordinates responses involving a variety of cells and molecules to protect us from invading pathogens, as well as cancer cells and foreign agents [13,14].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

Cruz¹,

Rodríguez-Fragoso²,

JorgeReyes-Esparza³

et al. 2018

Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications

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Nanotechnology currently plays a pivotal role in several fields and has enabled substantial advances in a relatively short time. In biomedicine, nanomaterials can be potentially employed as a tool for early diagnosis and an innovative mode of drug delivery. Novel nanomaterials are currently widely manipulated without a full assessment of their potential health risks. It is commonly thought that nanomaterials' first contact with the organism is through the different components of the immune system. However, if the entry route is intravenous, the first contact will be with the blood's components (erythrocytes, platelets, white cells, plasma and complement proteins). The presence of nanomaterials within a dynamic environment such as the bloodstream can produce potential harmful effects following interaction with several blood components. The design of innovative strategies leading to the development of more hemocompatible nanomaterials is also necessary.

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“…While the underlying mechanisms are not fully elucidated, anti-oxidative and anti-inflammatory effects are known to play a role 38). In leukocytes, important immune system components that are essential for inflammatory responses, the mitochondrial transmembrane potential, a functional marker of energy status and viability, is thought to be affected by regular exercise 910). It is possible that regular activity enhances the immune system and attenuates inflammatory responses by enhancing leukocyte mitochondrial functions,11) but, to date, no study of this relationship in peripheral lymphocytes has been reported.…”

Section: Introductionmentioning

confidence: 99%

Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women

et al. 2016

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BackgroundPrevious studies suggest that habitual exercise can improve skeletal mitochondrial function; however, to date, the association between exercise and mitochondrial function in peripheral leukocytes has not been reported. The aim of this study was to evaluate the relationship between regular exercise and mitochondrial function by measuring leukocyte mitochondrial DNA (mtDNA) copy number in postmenopausal women.MethodsThis cross-sectional study included 144 relatively healthy, non-diabetic, non-smoking, postmenopausal women. Clinical parameters, including anthropometric measurements and cardio-metabolic parameters, were assessed. Regular exercise was defined as at least 150 minutes per week of moderate-intensity activity, or an equivalent combination of moderate and vigorous-intensity activity, over a duration of at least 6 months. Leukocyte mtDNA copy numbers were measured using real-time polymerase chain reaction assays, and these were normalized to the β-globin copy number to give the relative mtDNA copy number.ResultsThe mtDNA copy number of peripheral leukocytes was significantly greater in the exercise group (1.33±0.02) than in the no exercise group (1.05±0.02, P<0.01). Stepwise multiple regression analysis showed that regular exercise was independently associated with mtDNA copy number (β=0.25, P<0.01) after adjusting for the variables age, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, homeostasis model assessment of insulin resistance value, and levels of high-density lipoprotein cholesterol, triglycerides, and homocysteine.ConclusionRegular exercise is associated with greater leukocyte mtDNA copy number in postmenopausal women.

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The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is “Inflammation” Always Inflammation?

Cited by 69 publications

References 135 publications

The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury

The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1–mediated tissue injury

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women

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