NFAT2 cytokine

OBJECTIVES: By using GWAS(genome-wide association studies) and linkage disequilibrium analysis to investigate the susceptibility genes of KD(Kawasaki disease), previous studies have identified that the CaN(calcineurin)-NFAT(the nuclear factor of activated T cell) signal pathway were significantly associated with susceptibility to KD. However, little is known about the molecular basis of the CaN/NFAT pathway involved in KD. Therefore, in our study we investigate the role of Ca2+/CaN/NFAT signaling pathway in macrophages in vitro and in vivo on coronary artery lesions induced by LCWE (Lactobacillus casei cell wall extract)...

HIV-1 infection leads to a gradual loss of T helper cells, chronic immune activation, and eventual immune system breakdown. HIV-1 causes deregulation of the expression of IL-2, a cytokine important for T helper cell growth and survival, which is downregulated in HIV-1 patients. The present study addresses the regulation of IL2 expression via HIV-1 Tat transcriptional activator. We used J-LAT cells, a T cell line that serves as a latency model for studies of HIV-1 expression in T cells, and as controls a T cell line lacking HIV-1 elements and a T cell line with a stably integrated copy of the HIV-1-LTR promoter...

Sustained expression of programmed cell death receptor-1 (PD-1) is correlated with the exhaustion of T cells, and blockade of the PD-1 pathway is an effective immunotherapeutic strategy for treating various cancers. However, response rates are limited, and many patients do not achieve durable responses. Thus, it is important to seek additional strategies that can improve anticancer immunity. Here, we report that the bromodomain and extraterminal domain (BET) inhibitor JQ1 inhibits PD-1 expression in Jurkat T cells, primary T cells, and T-cell exhaustion models...

The use of minipigs (Sus scrofa) as a platform for toxicological and pharmacological research is well established. In the present study, we investigated the effect of formaldehyde (FA) exposure on helper T cell-mediated splenic immune responses in Yucatan minipigs. The minipigs were exposed to different inhaled concentrations of FA (0, 2.16, 4.62, or 10.48 mg/m3 ) for a period of 2 weeks. Immune responses elicited by exposure to FA were determined by assessing physiological parameters, mRNA expression, and cytokine production...

Acute kidney injury (AKI) with maladaptive tubular repair leads to renal fibrosis and progresses to chronic kidney disease (CKD). At present, there is no curative drug to interrupt AKI-to-CKD progression. The nuclear factor of the activated T cell (NFAT) family was initially identified as a transcription factor expressed in most immune cells and involved in the transcription of cytokine genes and other genes critical for the immune response. NFAT2 is also expressed in renal tubular epithelial cells (RTECs) and podocytes and plays an important regulatory role in the kidney...

Th2 and Th17 immune response contribute to allergic rhinitis (AR) development. Targeting Th2 and Th17 response has been shown to ameliorate AR. Ibrutinib is an inhibitor for IL2-inducible T-cell kinase, which can promote Th2 and Th17 immune response. We sought to investigate the effect of ibrutinib on AR and the underlying mechanisms. We established house dust mite-induced AR mouse model and treated AR mice with ibrutinib. The symptoms of AR, serum level of immunoglobulin E, percentage of Th1, Th2, Th17, and Treg in nasal lymphoid tissues were monitored...

Programmed cell death-1 (PD-1) is a co-inhibitory receptor that dampens immune responses upon interaction with PD-L1 and PD-L2. Although PD-1 expression on T cells is known to be activation-dependent, how cytokines modify its regulation is not fully resolved. Using polyclonal T-cell activation to study cytokine-dependent PD-1 regulation, we found that IL-2 inhibited transcriptional up-regulation of PD-1 despite the promotion of T-cell activation. The IL-2-mediated reduction in PD-1 expression augmented CD8+ T-cell activities against PD-L1-expressing target cells...

T cell dysfunction is a common characteristic in leukemia patients that significantly impacts clinical treatment and prognosis. However, the mechanism underlying T cell dysfunction and its reversal remains unclear. In this study, in accordance with our previous findings, we found that the expression of NFAT2 and pri-miR-17 ~ 92 are lower in peripheral blood CD3+ T cells from chronic myelogenous leukemia (CML) patients by gene expression analysis. We further demonstrate that the NFAT2-induced activation, differentiation, and expression of cytokines in human umbilical cord blood CD8+ naïve T cells are miR-20a-5p dependent...

Transcription factor Ets-2 downregulates the expression of cytokine genes and HIV-1 in resting T-cells. Herein, we studied whether Ets-2 regulates the expression of lymphotropic factors (LFs) NFAT2, NF-κΒ/p65, c-Jun, c-Fos, which regulate the activation/differentiation of T-cells, and kinase CDK10, which controls Ets-2 degradation and repression activity. In silico analysis revealed Ets-2 binding sites on the promoters of NFAT2, c-Jun, c-Fos. The T-cell lines Jurkat (models T-cell signaling/activation) and H938 (contains the HIV-1-LTR) were transfected with an Ets-2 overexpressing vector, in the presence/absence of mitogens...

The mitochondria-to-nucleus retrograde signaling (MtRS) pathway aids in cellular adaptation to stress. We earlier reported that the Ca2+ - and calcineurin-dependent MtRS induces macrophage differentiation to bone-resorbing osteoclasts. However, mechanisms through which macrophages sense and respond to cellular stress remain unclear. Here, we induced mitochondrial stress in macrophages by knockdown (KD) of subunits IVi1 or Vb of cytochrome c oxidase (CcO). Whereas both IVi1 and Vb KD impair CcO activity, IVi1 KD cells produced higher levels of cellular and mitochondrial reactive oxygen species with increased glycolysis...

Nuclear factor of activated T cells (NFAT) transcription factors are required for induction of T-cell cytokine production and effector function. Although it is known that activation via the T-cell antigen receptor (TCR) results in 2 critical steps, calcineurin-mediated NFAT1 dephosphorylation and NFAT2 up-regulation, the molecular mechanisms underlying each are poorly understood. Here we find that T cell p38, which is activated by an alternative pathway independent of the mitogen-activated protein (MAP) kinase cascade and with different substrate specificities, directly controls these events...

The NFAT family transcription factors play crucial roles in immunological and other biological activities. NFAT3 is rarely expressed in T cells, and the mechanisms and significance of the specific NFAT3 downregulation in T cells have been unknown. In human CD4+ T cells, overexpression of NFAT1 and NFAT3 enhanced and suppressed IL-2 expression, respectively. NFAT3 downregulation in Jurkat cells using RNA interference technology augmented IL-2 expression, whereas a knockdown of NFAT1, NFAT2, and NFAT4 suppressed it...

Antitubulin chemotherapeutics agents, such as paclitaxel, are effective chemotherapy drugs for cancer treatment. However, painful neuropathy is a major adverse effect limiting the wider application of chemotherapeutics. In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150flox/flox in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment...

Background. The etiology of immune reconstitution inflammatory syndrome (IRIS) in AIDS patients after the initiation of HAART remains unknown. Several researches indicated that the development of IRIS is associated with the production and variation of cytokines, whose gene expression are closely related to the Ca2(+)/CN-nuclear factor of activated T cells (NFAT) pathway. Methods. We studied the expression of NFAT isoforms and their major target cytokines genes in peripheral blood CD3(+) T cells of subjects through fluorescence quantitative PCR and explored the expression changes of these genes before and after HAART...

Interleukin (IL)-25, also known as IL-17E, belongs to the IL-17 family of cytokines. Unlike other IL-17 family members, IL-25 promotes Th2-type immune responses, stimulating IL-4, IL-5, and IL-13 production. Here, we employed murine models of skin graft to explore the role of IL-25 in suppression of graft rejection. We found that IL-25 expression is increased during allograft rejection, and allograft rejection was enhanced in IL-25 KO mice. IL-25 KO was associated with down-regulation of Foxp3 expression in CD4+ T cells...

Hepatitis B virus (HBV) infection is the major cause of inflammatory liver disease, of which the clinical recovery and effective anti-viral therapy is associated with the sustained viral control of effector T cells. In humans, chronic HBV infection often shows weak or absent virus-specific T-cell reactivity, which is described as the 'exhaustion' state characterized by poor effector cytotoxic activity, impaired cytokine production and sustained expression of multiple inhibitory receptors, such as programmed cell death-1 (PD-1), lymphocyte activation gene-3, cytotoxic T lymphocyte-associated antigen-4 and CD244...

Abstract Alpinetin, a flavonoid compound extracted from the seeds of Alpinia katsumadai Hayata, has been known to possess antibacterial, anti-inflammatory and other important therapeutic activities. In the current study, we investigated alpinetin for its immunosuppressive effect on activation and cytokines secretion of murine T lymphocytes. The data showed that alpinetin markedly suppressed ConA-induced murine splenocyte proliferation, Th1/Th2 cytokines production, CD4(+) T-cell populations and ratio of CD4(+)/CD8(+)...

The mechanisms controlling the switch between the pro-angiogenic and pro-inflammatory states of endothelial cells are still poorly understood. In this paper, we show that: (a) COX-2 expression induced by VEGF-A is NFAT2-dependent; and (b) the integrin profile in endothelial cells induced by the pro-angiogenic VEGF-A is distinct from that brought on by the inflammatory cytokine TNF-α. Two groups of integrin subunits specifically upregulated over time by both cytokines were identified using RT-PCR and Western Immunoblotting...

Farrerol, a new type of 2,3-dihydro-flavonoid, has been isolated from the leaves of Rhododendron dauricum L. In the present study, we found that farrerol exerted potent immunosuppressive effects on murine T cells both in vitro and in vivo. In vitro, farrerol markedly suppressed concanavalin A (ConA)-induced lymphocyte proliferation, Th1 and Th2 cytokine production, cluster of differentiation 4-positive (CD4(+)) T cell populations, and the ratio of CD4(+)/cluster of differentiation 8-positive (CD8(+)) T cells...

BACKGROUND: The NFAT family transcription factors play crucial roles in T cell functions. Recently, NFAT has been implicated in the production of an inflammatory cytokine, IL-17A; however, functional differences among NFAT members in IL-17A synthesis have not been elucidated. In this study, the relative contribution of NFAT1 and NFAT2 to IL-17A expression in human T cells was investigated. METHODS: NFAT1 and NFAT2 were introduced in human cord blood CD4+ T cells by a lentiviral transduction system...