scholarly journals Aquaporins in Immune Cells and Inflammation: New Targets for Drug Development

2021 ◽  
Vol 22 (4) ◽  
pp. 1845
Author(s):  
Inês V. da Silva ◽  
Graça Soveral

The mammalian immune system senses foreign antigens by mechanisms that involve the interplay of various kinds of immune cells, culminating in inflammation resolution and tissue clearance. The ability of the immune cells to communicate (via chemokines) and to shift shape for migration, phagocytosis or antigen uptake is mainly supported by critical proteins such as aquaporins (AQPs) that regulate water fluid homeostasis and volume changes. AQPs are protein channels that facilitate water and small uncharged molecules’ (such as glycerol or hydrogen peroxide) diffusion through membranes. A number of AQP isoforms were found upregulated in inflammatory conditions and are considered essential for the migration and survival of immune cells. The present review updates information on AQPs’ involvement in immunity and inflammatory processes, highlighting their role as crucial players and promising targets for drug discovery.

2016 ◽  
Vol 7 (2) ◽  
pp. 275-287 ◽  
Author(s):  
A.A. Van Beek ◽  
J.A. Hoogerland ◽  
C. Belzer ◽  
P. De Vos ◽  
W.M. De Vos ◽  
...  

Probiotics influence the immune system, both at the local and systemic level. Recent findings suggest the relation between microbiota and the immune system alters with age. Our objective was to address direct effects of six bacterial strains on immune cells from young and aged mice: Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, Lactococcus lactis MG1363, Bifidobacterium breve ATCC15700, Bifidobacterium infantis ATCC15697, and Akkermansia muciniphila ATCC BAA-835. We used splenocytes and naïve or interferon-γ-stimulated bone marrow-derived macrophages (BMDM) as responder populations. All tested bacterial strains induced phenotypic and cytokine responses in splenocytes and BMDM. Based on magnitude of the cellular inflammatory response and cytokine profiles, two subgroups of bacteria were identified, i.e. L. plantarum and L. casei versus B. breve, B. infantis, and A. muciniphila. The latter group of bacteria induced high levels of cytokines produced under inflammatory conditions, including tumour necrosis factor (TNF), interleukin (IL)-6 and IL-10. Responses to L. lactis showed features of both subgroups. In addition, we compared responses by splenocytes and BMDM derived from young mice to those of aged mice, and found that splenocytes and BMDM derived from aged mice had an increased IL-10 production and dysregulated IL-6 and TNF production compared to young immune cells. Overall, our study shows differential inflammatory responses to distinct bacterial strains, and profound age-dependent effects. These findings, moreover, support the view that immune environment importantly influences bacterial immune effects.


2021 ◽  
Author(s):  
Olga Schweigert ◽  
Julia Adler ◽  
Natalie Längst ◽  
Dylan Aïssi ◽  
Jorge Duque Escobar ◽  
...  

Hypertension is a complex and multifactorial disorder caused by lifestyle and environmental factors, inflammation and disease-related genetic factors and is a risk factor for stroke, ischemic heart disease and renal failure. Although circulating monocytes and tissue macrophages contribute to the pathogenesis of hypertension, the underlying mechanisms are poorly understood. Cysteine rich protein 1 (CRIP1) is highly expressed in immune cells, and CRIP1 mRNA expression in monocytes associates with blood pressure (BP) and is upregulated by proinflammatory modulation suggesting a link between CRIP1 and BP regulation through the immune system. To address this functional link, we studied CRIP1 expression in immune cells in relation to BP using a human cohort study and hypertensive mouse models. CRIP1 expression in splenic monocytes/macrophages and in circulating monocytes was significantly affected by angiotensin II (Ang II) in a BP-elevating dose (2 mg/kg/day). In the human cohort study, monocytic CRIP1 expression levels were associated with elevated BP, whereas upon differentiation of monocytes to macrophages this association along with the CRIP1 expression level was diminished. In conclusion, CRIP1-positive circulating and splenic monocytes seem to play an important role in hypertension related inflammatory processes through endogenous hormones such as Ang II. These findings suggest that CRIP1 may affect the interaction between the immune system, in particular monocytes, and the pathogenesis of hypertension.


2019 ◽  
Vol 26 (6) ◽  
pp. 1027-1044 ◽  
Author(s):  
Giulia Freer ◽  
Fabrizio Maggi ◽  
Mauro Pistello

Background:The virome is a network of viruses normally inhabiting humans. It forms a conspicuous portion of the so-called microbiome, once generically referred to as resident flora. Indeed, viruses infecting humans without leading to clinical disease are increasingly recognized as part of the microbiome and have an impact on the development of our immune system. In addition, they activate inflammasomes, multiprotein complexes that assemble in cells and that are responsible for the downstream effects of sensing pathogens.Objective:This review aims at summarizing the evidence on the role of the virome in modulating inflammation and emphasizes evidence for Anelloviruses as useful molecular markers to monitor inflammatory processes and immune system competence.Method:We carried out a review of the literature published in the last 5 years and summarized older literature to take into account ground-breaking discoveries concerning inflammasome assembly and virome.Results:A massive amount of data recently emerging demonstrate that the microbiome closely reflects what we eat, and many other unexpected variables. Composition, location, and amount of the microbiome have an impact on innate and adaptive immune defences. Viruses making up the virome contribute to shaping the immune system. Anelloviruses, the best known of such viruses, are present in most human beings, persistently without causing apparent disease. Depending on their interplay with such viruses, inflammasomes instruct host defences to tolerate or forfeit a specific microorganism.Conclusion:The virome plays an important role in shaping human immune defences and contributes to inflammatory processes by quenching or increasing them.


2019 ◽  
Vol 20 (8) ◽  
pp. 799-816 ◽  
Author(s):  
Yue Qiu ◽  
Guo-wei Tu ◽  
Min-jie Ju ◽  
Cheng Yang ◽  
Zhe Luo

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.


Author(s):  
Caterina Ledda ◽  
Claudia Lombardo ◽  
Elisabetta A. Tendi ◽  
Maria Hagnas ◽  
Gianluca Paravizzini ◽  
...  

: Fluoro-edenite (FE) is an asbestos-like amphibole present in the bentonitic lavas extracted from a stone quarry in Biancavilla, a village sited in the Etnean Volcanic Area (Italy). : Thoracic pathologies are the results of excessive inflammatory processes that are the early response of the immune system to inhaled fibers. As demonstrated for asbestos, fibers may trigger immune system cells in an acute and/or chronic manner. This review aims to clarify the pathways of inflammation in workers exposed to FE fibers. : Based on the articles reviewed, it seems that a permanent stimulus created by repeatedly inhaling the FE fibers and their persistence in the body can act as trigger both in promoting inflammatory processes and in immunological induction of autoimmune disease.


2020 ◽  
Vol 20 (9) ◽  
pp. 1523-1530
Author(s):  
Murat Dabak ◽  
Durrin O. Dabak ◽  
Tuncay Kuloglu ◽  
Ersoy Baydar ◽  
Hakan Bulut ◽  
...  

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.


Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.


2006 ◽  
Vol 13 (4) ◽  
pp. 141-143 ◽  
Author(s):  
T. Hahn ◽  
Emmanuel Akporiaye

Human tumours have evolved intricate mechanisms to evade the immune system, either by avoiding recognition or by inhibiting and eliminating immune cells. [...]


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 730
Author(s):  
Moritz Peiseler ◽  
Frank Tacke

Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.


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