Understanding the Role of Antiviral Cytokines and Chemokines on Neural Stem/Progenitor Cell Activity and Survival

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

Download Full-text

Neuronal guidance proteins in cardiovascular inflammation

Basic Research in Cardiology ◽

10.1007/s00395-021-00847-x ◽

2021 ◽

Vol 116 (1) ◽

Author(s):

Marius Keller ◽

Valbona Mirakaj ◽

Michael Koeppen ◽

Peter Rosenberger

Keyword(s):

Cell Activation ◽

Immune Cell ◽

Vascular Endothelial ◽

Therapeutic Approaches ◽

Immune Cell Activation ◽

Cytokines And Chemokines ◽

The Future ◽

Cardiovascular Pathologies ◽

Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

Download Full-text

CD206+ macrophage is an accelerator of endometriotic-like lesion via promoting angiogenesis in the endometriosis mouse model

Scientific Reports ◽

10.1038/s41598-020-79578-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yosuke Ono ◽

Osamu Yoshino ◽

Takehiro Hiraoka ◽

Erina Sato ◽

Akiko Furue ◽

...

Keyword(s):

Mouse Model ◽

Diphtheria Toxin ◽

Immunohistochemical Study ◽

Mrna Levels ◽

Cytokines And Chemokines ◽

Diphtheria Toxin Receptor ◽

Endothelial Cell Marker ◽

Toxin Receptor ◽

Group A

AbstractIn endometriosis, M2 MΦs are dominant in endometriotic lesions, but the actual role of M2 MΦ is unclear. CD206 positive (+) MΦ is classified in one of M2 type MΦs and are known to produce cytokines and chemokines. In the present study, we used CD206 diphtheria toxin receptor mice, which enable to deplete CD206+ cells with diphtheria toxin (DT) in an endometriosis mouse model. The depletion of CD206+ MΦ decreased the total weight of endometriotic-like lesions significantly (p < 0.05). In the endometriotic-like lesions in the DT group, a lower proliferation of endometriotic cells and the decrease of angiogenesis were observed. In the lesions, the mRNA levels of VEGFA and TGFβ1, angiogenic factors, in the DT group significantly decreased to approximately 50% and 30% of control, respectively. Immunohistochemical study revealed the expressions of VEGFA and an endothelial cell marker CD31 in lesions of the DT group, were dim compared to those in control. Also, the number of TGFβ1 expressing MΦ was significantly reduced compared to control. These data suggest that CD206+ MΦ promotes the formation of endometriotic-like lesions by inducing angiogenesis around the lesions.

Download Full-text

The Role of NKT Cells in Glioblastoma

Cells ◽

10.3390/cells10071641 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1641

Author(s):

Emily E. S. Brettschneider ◽

Masaki Terabe

Keyword(s):

Immune Responses ◽

Cell Activity ◽

Nkt Cells ◽

Type I ◽

Type Ii ◽

Central Nervous System Diseases ◽

Nkt Cell ◽

Lipid Antigens ◽

Immunoregulatory Mechanisms

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

Download Full-text

T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽

10.1177/0961203319877242 ◽

2019 ◽

Vol 28 (12) ◽

pp. 1468-1472 ◽

Cited By ~ 2

Author(s):

N Yoshida ◽

F He ◽

V C Kyttaris

Keyword(s):

T Cells ◽

T Cell ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Cell Responses ◽

Cytokines And Chemokines ◽

Novel Approach ◽

Cell Tissue ◽

External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

Download Full-text

TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00711-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Xueer Wang ◽

Honghai Zhang ◽

Zhugui Shao ◽

Wanxin Zhuang ◽

Chao Sui ◽

...

Keyword(s):

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Fungal Pathogen ◽

Essential Role ◽

Molecular Mechanisms ◽

Systemic Infection ◽

Lectin Receptors ◽

Innate And Adaptive Immunity ◽

Cytokines And Chemokines

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

Download Full-text

ROLE OF A GENETIC REGION ON CHROMOSOME 4 IN THE REGULATION OF NATURAL KILLER CELL ACTIVITY IN MICE

European Journal of Immunogenetics ◽

10.1111/j.1744-313x.1993.tb00157.x ◽

1993 ◽

Vol 20 (5) ◽

pp. 381-389

Author(s):

D.P. Dubey ◽

N.M. Mirza ◽

B.I. Zaharian ◽

E.J. Yunis

Keyword(s):

Natural Killer Cell ◽

Natural Killer ◽

Natural Killer Cell Activity ◽

Killer Cell ◽

Cell Activity ◽

Chromosome 4 ◽

Genetic Region ◽

Killer Cell Activity

Download Full-text

An Examination of the Role of Transcriptional and Posttranscriptional Regulation in Rhabdomyosarcoma

Stem Cells International ◽

10.1155/2017/2480375 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Alexander J. Hron ◽

Atsushi Asakura

Keyword(s):

Skeletal Muscle ◽

Soft Tissue ◽

Posttranscriptional Regulation ◽

Progenitor Cell ◽

Treatment Options ◽

Soft Tissue Tumors ◽

Basic Helix Loop Helix ◽

Helix Loop Helix ◽

Bhlh Proteins

Rhabdomyosarcoma (RMS) is an aggressive family of soft tissue tumors that most commonly manifests in children. RMS variants express several skeletal muscle markers, suggesting myogenic stem or progenitor cell origin of RMS. In this review, the roles of both recently identified and well-established microRNAs in RMS are discussed and summarized in a succinct, tabulated format. Additionally, the subtypes of RMS are reviewed along with the involvement of basic helix-loop-helix (bHLH) proteins, Pax proteins, and microRNAs in normal and pathologic myogenesis. Finally, the current and potential future treatment options for RMS are outlined.

Download Full-text