scholarly journals Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

2021 ◽  
Vol 22 (3) ◽  
pp. 1347
Author(s):  
Anaïs Amend ◽  
Natalie Wickli ◽  
Anna-Lena Schäfer ◽  
Dalina T. L. Sprenger ◽  
Rudolf A. Manz ◽  
...  

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

Author(s):  
Asmaa Nabil-Adam ◽  
Mohamed A. Shreadah

Background: This study aimed to investigate the potential bioactivity and the ameliorative role of Galaxaura oblongata (G. oblongata) against LPS-induced toxicity by using hematological parameters. Objective: It is aimed also to examine its protective effect using the immunohistochemistry of liver and lungs as biomarkers in male BALB/C albino mice. Materials and Methods: the current study carried out using different in-vitro and in-vivo assays such as phytochemical, antioxidants, anti-inflammatory for in-vitro where the hematological and immunohistochemistry for lung and liver were investigated in vivo. Results: There are no previous studies were performed to investigate the in vivo and in vitro effects of the G. oblongata extracts as antioxidant and anti-inflammatory due to their rareness compared to other red algae. LPS treated mice revealed a significant decrease in total number of WBCs, RBCs, platelets, and HGB%, MPV, MCV and MCHC compared to the control group. On contrast, the HCT and MCHC were increased in the induction group which was treated with LPS compared to the control group. Furthermore, the immunohistochemistry results of the present study revealed the protective effect of G. oblongata compared to the induction group. G. oblongata can be used as protective marine natural products against the toxicity induced by LPS. Conclusion: It exhibited a significant ameliorative role against the alterations in the hematological parameters and immunohistochemistry of liver and lungs, and helps to reduce as well as coordinate the acute inflammations caused by TNF.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Chanwoo Kim ◽  
Hannah Song ◽  
Sandeep Kumar ◽  
Douglas Nam ◽  
Hyuk Sang Kwon ◽  
...  

Atherosclerosis is a multifactorial disease that arises from a combination of endothelial dysfunction and inflammation, occurring preferentially in arterial regions exposed to disturbed flow. Bone morphogenic protein-4 (BMP4) produced by disturbed flow induces inflammation, endothelial dysfunction and hypertension, suggesting the importance of BMPs in vascular biology and disease. BMPs bind to two different types of BMP receptors (BMPRI and II) to instigate intracellular signaling. Increasing evidences suggest a correlative role of BMP4 and atherosclerosis, but the role of BMP receptors especially BMPRII in atherosclerosis is still unclear and whether knockdown of BMPRII is the cause or the consequence of atherosclerosis is still not known. It is therefore, imperative to investigate the mechanisms by which BMPRII expression is modulated and its ramifications in atherosclerosis. Initially, we expected that knockdown of BMPRII will result in loss of pro-atherogenic BMP4 signaling and will thereby prevent atherosclerosis. Contrarily, we found that loss of BMPRII expression causes endothelial inflammation and atherosclerosis. Using BMPRII siRNA and BMPRII +/- mice, we found that BMPRII knockdown induces endothelial inflammation in a BMP-independent manner via mechanisms involving reactive oxygen species (ROS), NFκB, and NADPH oxidases. Further, BMPRII +/- ApoE -/- mice develop accelerated atherosclerosis compared to BMPRII +/+ ApoE -/- mice, suggesting loss of BMPRII may induce atherosclerosis. Interestingly, we found that multiple pro-atherogenic stimuli such as hypercholesterolemia, disturbed flow, pro-hypertensive angiotensin II, and pro-inflammatory cytokine, TNFα, downregulate BMPRII expression in endothelium, while anti-atherogenic stimuli such as stable flow and statin treatment upregulate its expression, both in vivo and in vitro . Moreover, we found that BMPRII expression is significantly diminished in human coronary advanced atherosclerotic lesions. These results suggest that BMPRII is a critical, anti-inflammatory and anti-atherogenic protein that is commonly targeted by multiple pro- and anti-atherogenic factors. BMPRII could be used as a novel diagnostic and therapeutic target in atherosclerosis.


2019 ◽  
Vol 47 (5) ◽  
pp. 516-524 ◽  
Author(s):  
Dafne Garcia-Mateos ◽  
Alba Maria Garcia-Lino ◽  
Indira Alvarez-Fernandez ◽  
Esther Blanco-Paniagua ◽  
Alvaro de la Fuente ◽  
...  

2016 ◽  
Vol 311 (3) ◽  
pp. L664-L675 ◽  
Author(s):  
Clémence O. Henry ◽  
Emilie Dalloneau ◽  
Maria-Teresa Pérez-Berezo ◽  
Cristina Plata ◽  
Yongzheng Wu ◽  
...  

Cystic fibrosis (CF) is an inherited disease associated with chronic severe lung inflammation, leading to premature death. To develop innovative anti-inflammatory treatments, we need to characterize new cellular and molecular components contributing to the mechanisms of lung inflammation. Here, we focused on the potential role of “transient receptor potential vanilloid-4” (TRPV4), a nonselective calcium channel. We used both in vitro and in vivo approaches to demonstrate that TRPV4 expressed in airway epithelial cells triggers the secretion of major proinflammatory mediators such as chemokines and biologically active lipids, as well as a neutrophil recruitment in lung tissues. We characterized the contribution of cytosolic phospholipase A2, MAPKs, and NF-κB in TRPV4-dependent signaling. We also showed that 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids, i.e., four natural lipid-based TRPV4 agonists, are present in expectorations of CF patients. Also, TRPV4-induced calcium mobilization and inflammatory responses were enhanced in cystic fibrosis transmembrane conductance regulator-deficient cellular and animal models, suggesting that TRPV4 is a promising target for the development of new anti-inflammatory treatments for diseases such as CF.


2004 ◽  
Vol 13 (5-6) ◽  
pp. 365-368 ◽  
Author(s):  
Elzbieta Stankiewicz ◽  
Ewa Wypasek ◽  
Barbara Plytycz

BACKGROUND and aim: Morphine co-injection has anti-inflammatory effects on zymosan-induced peritonitis in several strains of mice except that of CBA. As peritoneal mast cells (pMCs) are much more numerous in CBA mice than in SWISS mice, the role of pMCs in morphine-modulated zymosan peritonitis is compared in CBA and SWISS males.Methods: pMCs were treatedin vitrowith morphine or C48/80 for comparison of histamine release.In vivoaccumulation of leukocytes and histamine in peritoneal exudate were recorded after intraperitoneal injection with morphine, zymosan, or zymosan plus morphine.Results and conclusion: Morphine induces histamine release by pMCs from CBA mice but not SWISS mice.In vivomorphine-induced peritonitis is stronger in CBA mice than SWISS mice. Corollary, morphine anti-inflammatory effects on zymosan peritonitis are reversed in CBA mice by its pro-inflammatory action through CBA pMCs.


1993 ◽  
Vol 178 (1) ◽  
pp. 257-264 ◽  
Author(s):  
K H Grabstein ◽  
T J Waldschmidt ◽  
F D Finkelman ◽  
B W Hess ◽  
A R Alpert ◽  
...  

The effects of interleukin 7 (IL-7) on the growth and differentiation of murine B cell progenitors has been well characterized using in vitro culture methods. We have investigated the role of IL-7 in vivo using a monoclonal antibody that neutralizes IL-7. We find that treatment of mice with this antibody completely inhibits the development of B cell progenitors from the pro-B cell stage forward. We also provide evidence that all peripheral B cells, including those of the B-1 and conventional lineages, are derived from IL-7-dependent precursors. The results are consistent with the rapid turnover of B cell progenitors in the marrow, but a slow turnover of mature B cells in the periphery. In addition to effects on B cell development, anti-IL-7 treatment substantially reduced thymus cellularity, affecting all major thymic subpopulations.


2007 ◽  
Vol 98 (S1) ◽  
pp. S24-S28 ◽  
Author(s):  
Carlos Muñoz ◽  
Ernesto Rios ◽  
Jorge Olivos ◽  
Oscar Brunser ◽  
Manuel Olivares

Microminerals including copper and iron are essential to immunity and health in human beings. The development of powerful tools in analytical cell biology and molecular genetics has facilitated efforts to identify specific cellular and molecular functions of trace elements in the maturation, activation and functions of host defence mechanisms. Selected recent reports about the role of copper and iron nutrition on immune functions are critically analysed here. Effects of trace element supplementation on infectious morbidity are also reviewed. While micromineral deficiencies, in general, may have widespread effects on nearly all components of immune response, these effects can be reversed by supplementation. However, the conflicting effects of iron deficiency and iron supplementationin vitroon the defensive systems reveals the urgent need for further additional information on thein vivosituation. In the elderly, vaccination against respiratory infections is likely to protect only 30–70 % of the population. However, it may be possible to modulate immune function and ultimately reduce the severity of infections through micronutrient supplementation. Thus, microminerals contribute to the maintenance of the balance between immunity and health in humans.


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