scholarly journals Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Takuya Kotani ◽  
Ryota Masutani ◽  
Takayasu Suzuka ◽  
Katsuhiro Oda ◽  
Shigeki Makino ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Injury ◽  
Mouse Model ◽  
Interstitial Pneumonia ◽  
Cell Number ◽  
Dependent Manner ◽  
Activated Macrophages ◽  
A Cell ◽  
Anti Inflammatory ◽  
Differentiation And Proliferation

Abstract Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner. AdSCs inhibited the production of pro-inflammatory cytokines such as TNF-α and IL-12 in activated macrophages, and AdSCs also induced the apoptosis of activated macrophages. AdSCs inhibited the differentiation and proliferation of Th2-type mCD4+ T cells but promoted the differentiation and proliferation of regulatory T cells, suggesting that the phenotypic conversion of T cells may be one of the mechanisms for the anti-inflammatory effect of AdSCs on pulmonary fibrosis. These findings suggest that intravenous AdSCs could be a promising treatment for patients with interstitial pneumonia.

Testosterone exerts selective anti-inflammatory effects on human skin mast cells in a cell subset dependent manner

2012 ◽  
Vol 21 (11) ◽  
pp. 878-880 ◽  
Author(s):  
Sven Guhl ◽  
Metin Artuc ◽  
Torsten Zuberbier ◽  
Magda Babina
Keyword(s):  
Mast Cells ◽  
Human Skin ◽  
Cell Subset ◽  
Dependent Manner ◽  
A Cell ◽  
Anti Inflammatory

Ulinastatin Activated The ERK5/Mer Signaling Pathway To Promote Macrophage Efferocytosis And Ameliorate Lung Inflammation

2021 ◽  
Author(s):  
Jinju Li ◽  
Rongge Shao ◽  
Qiuwen Xie ◽  
XueKe Du
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Lung Inflammation ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Dependent Manner ◽  
Anti Inflammatory

Abstract Purpose:Ulinastatin (UTI) is an endogenous protease inhibitor with potent anti-inflammatory, antioxidant and organ protective effects. The inhibitor has been reported to ameliorate inflammatory lung injury but precise mechanisms remain unclear. Methods: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). The number of neutrophils and the phagocytosis of apoptotic neutrophils were observed by Diff- Quick method. Lung injury was observed by HE staining .BALF cells were counted by hemocytometer and concentrations of protein plus inflammatory factors were measured with a BCA test kit. During in vitro experiments, RAW264.7 cells were pretreated with UTI (1000 and 5000U/ mL), stained with CellTrackerTM Green B0DIPYTM and HL60 cells added with UV-induced apoptosis and PKH26 Red staining. The expression of ERK5\Mer related proteins was detected by western blot and immunofluorescence.Results: An in vivo model of lung injury has been constructed by intratracheal infusion of lipopolysaccharide (LPS). UTI treatment enhanced the phagocytotic effect of mouse alveolar macrophages on neutrophils, alleviated lung lesions, decreased the pro-inflammatory factor and total protein content of BALF and increased levels of anti-inflammatory factors. in vitro experiments ，UTI enhanced the phagocytosis of apoptotic bodies by RAW264.7 cells in a dose-dependent manner. Increased expression levels of ERK5 and Mer by UTI were shown by Western blotting and immunofluorescence.Conclusions: UTI mediated the activation of the ERK5/Mer signaling pathway, enhanced phagocytosis of neutrophils by macrophages and improved lung inflammation. The current study indicates potential new clinical approaches for accelerating the recovery from lung inflammation.

scholarly journals Regulatory T Cell Suppression Is Potentiated by Target T Cells in a Cell Contact, IL-35- and IL-10-Dependent Manner

2009 ◽  
Vol 182 (10) ◽  
pp. 6121-6128 ◽  
Author(s):  
Lauren W. Collison ◽  
Meenu R. Pillai ◽  
Vandana Chaturvedi ◽  
Dario A. A. Vignali
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Cell Contact ◽  
Dependent Manner ◽  
T Cell Suppression ◽  
A Cell ◽  
Cell Suppression

scholarly journals MR1-Restricted T Cells in Cancer Immunotherapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2145
Author(s):  
Pedro Flores-Villanueva ◽  
Navid Sobhani ◽  
Xu Wang ◽  
Yong Li
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Acid Synthesis ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Mait Cells ◽  
Mucosal Tissues ◽  
Wide Range ◽  
A Cell ◽  
Cell Membrane Protein

Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells’ TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.

scholarly journals 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shan-Ting Liao ◽  
Chao Han ◽  
Ding-Qiao Xu ◽  
Xiao-Wei Fu ◽  
Jun-Song Wang ◽  
...  
Keyword(s):  
Aerobic Glycolysis ◽  
Glycolytic Enzyme ◽  
Cysteine Residue ◽  
Glycolytic Flux ◽  
Flux Analysis ◽  
Activated Macrophages ◽  
A Cell ◽  
Anti Inflammatory ◽  
Heptelidic Acid

Abstract Activated macrophages switch from oxidative phosphorylation to aerobic glycolysis, similar to the Warburg effect, presenting a potential therapeutic target in inflammatory disease. The endogenous metabolite itaconate has been reported to regulate macrophage function, but its precise mechanism is not clear. Here, we show that 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) directly alkylates cysteine residue 22 on the glycolytic enzyme GAPDH and decreases its enzyme activity. Glycolytic flux analysis by U13C glucose tracing provides evidence that 4-OI blocks glycolytic flux at GAPDH. 4-OI thereby downregulates aerobic glycolysis in activated macrophages, which is required for its anti-inflammatory effects. The anti-inflammatory effects of 4-OI are replicated by heptelidic acid, 2-DG and reversed by increasing wild-type (but not C22A mutant) GAPDH expression. 4-OI protects against lipopolysaccharide-induced lethality in vivo and inhibits cytokine release. These findings show that 4-OI has anti-inflammatory effects by targeting GAPDH to decrease aerobic glycolysis in macrophages.

scholarly journals Piperine Plays an Anti-Inflammatory Role inStaphylococcus aureusEndometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Wen-jun Zhai ◽  
Zhen-biao Zhang ◽  
Nian-nian Xu ◽  
Ying-fang Guo ◽  
Changwei Qiu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Biological Activities ◽  
Dependent Manner ◽  
Pathogenic Microorganisms ◽  
Histopathological Changes ◽  
Natural Medicine ◽  
Anti Inflammatory ◽  
Dose Dependent

Endometritis is commonly caused by pathogenic microorganisms, includingStaphylococcus aureus(S. aureus). Piperine, which is a natural medicine, has shown a variety of biological activities. To explore the effect and mechanism of piperine onS. aureusendometritis, a mouse model ofS. aureusendometritis was successfully established in the present study. Histopathological changes were observed with H&E staining, cytokines were analyzed by ELISA, mRNA was analyzed by qPCR, and proteins were detected by western blot. The results showed that piperine could significantly alleviate inflammatory injury inS. aureusendometritis. The qPCR and ELISA results showed that piperine effectively reduced theS. aureus-induced overexpression of TNF-α, IL-1β, and IL-6 but increased the expression of IL-10. TheS. aureus-induced inflammation was related to TLR-2 and TLR-4 because the results showed that their expression was increased inS. aureusinfection but then decreased with piperine treatment. To further confirm that piperine caused an anti-inflammatory response by targeting NF-κB and MAPKs, the expression of I-κB, p65, p38, ERK, and JNK was measured. The phosphorylation of I-κB, p65, p38, ERK, and JNK was inhibited by piperine in a dose-dependent manner. All of the results indicated that piperine may be a potential anti-inflammatory drug both in endometritis and in otherS. aureus-induced diseases.

scholarly journals Inhibitory effects of α-Mangostin on T cell cytokine secretion via ORAI1 calcium channel and K+ channels inhibition

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10973
Author(s):  
Hyun Jong Kim ◽  
Seorin Park ◽  
Hui Young Shin ◽  
Yu Ran Nam ◽  
Phan Thi Lam Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ion Channels ◽  
Calcium Channel ◽  
Immune Cells ◽  
Potassium Ion ◽  
Cytokine Secretion ◽  
Potassium Ion Channels ◽  
Dependent Manner ◽  
Anti Inflammatory

Background As one of the main components of mangosteen (Garcinia mangostana), a tropical fruit, α-mangostin has been reported to have numerous pharmacological benefits such as anti-cancer, anti-inflammatory, and anti-allergic effects through various mechanisms of action. The effects of α-mangostin on intracellular signaling proteins is well studied, but the effects of α-mangostin on ion channels and its physiological effects in immune cells are unknown. Generation of intracellular calcium signaling is a fundamental step for T cell receptor stimulation. This signaling is mediated not only by the ORAI1 calcium channel, but also by potassium ion channels, which provide the electrical driving forces for generating sufficient calcium ion influx. This study investigated whether α-mangosteen suppress T cell stimulation by inhibiting ORAI1 and two kinds of potassium channels (Kv1.3 and KCa3.1), which are normally expressed in human T cells. Methods This study analyzed the inhibitory effect of α-mangostin on immune cell activity via inhibition of calcium and potassium ion channels expressed in immune cells. Results α-mangostin inhibited ORAI1 in a concentration-dependent manner, and the IC50 value was 1.27 ± 1.144 µM. Kv1.3 was suppressed by 41.38 ± 6.191% at 3 µM, and KCa3.1 was suppressed by 51.16 ± 5.385% at 3 µM. To measure the inhibition of cytokine secretion by immune cells, Jurkat T cells were stimulated to induce IL-2 secretion, and α-mangostin was found to inhibit it. This study demonstrated the anti-inflammatory effect of α-mangostin, the main component of mangosteen, through the regulation of calcium signals.

scholarly journals Feedback control of neurogenesis by tissue packing

2018 ◽  
Author(s):  
Tom W. Hiscock ◽  
Joel B. Miesfeld ◽  
Kishore R. Mosaliganti ◽  
Brian A. Link ◽  
Sean G. Megason
Keyword(s):  
Feedback Control ◽  
Cell Cycle Progression ◽  
Cell Number ◽  
Apical Surface ◽  
Dependent Manner ◽  
Tissue Architecture ◽  
Cycle Progression ◽  
Dense Tissue ◽  
Negative Feedback Control ◽  
Differentiation And Proliferation

AbstractBalancing the rate of differentiation and proliferation in developing tissues is essential to produce organs of robust size and composition. Whilst many molecular regulators have been established, how these connect to physical and geometrical aspects of tissue architecture is poorly understood. Here, using high-resolution timelapse imaging, we find that dense tissue packing and complex cell geometries play a significant role in regulating differentiation rate in the zebrafish neural tube. Specifically, in regions of high cell density, progenitors are physically pushed away from the apical surface, which, in a Notch-dependent manner, leads to their differentiation. Using simulations we show that this naturally performs negative feedback control on cell number. Our results suggest a model whereby differentiation rate is carefully tuned to correct fluctuations in cell number, originating from variable cell cycle progression and inherently probabilistic differentiation programs.

scholarly journals Sphingosine-1-phosphate receptor 2 restrains egress of γδ T cells from the skin

2019 ◽  
Vol 216 (7) ◽  
pp. 1487-1496 ◽  
Author(s):  
Brian J. Laidlaw ◽  
Elizabeth E. Gray ◽  
Yang Zhang ◽  
Francisco Ramírez-Valle ◽  
Jason G. Cyster
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Γδ T Cells ◽  
Dependent Manner ◽  
Γδ T Cell ◽  
T Cell Migration ◽  
Sphingosine 1 Phosphate ◽  
A Cell ◽  
Draining Lymph Node

Maintenance of a population of IL-17–committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1-phosphate receptor 2 (S1PR2) acts in a cell-intrinsic manner to oppose γδ T cell migration from the dermis to the skin draining lymph node (dLN). Migration of dermal γδ T cells to the dLN under steady-state conditions occurs in an S1PR1-dependent manner. S1PR1 and CD69 are reciprocally expressed on dermal γδ T cells, with loss of CD69 associated with increased S1PR1 expression and enhanced migration to the dLN. γδ T cells lacking both S1PR2 and CD69 are impaired in their maintenance within the dermis. These findings provide a mechanism for how IL-17+ γδ T cells establish residence within the dermis and identify a role for S1PR2 in restraining the egress of tissue-resident lymphocytes.

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