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Jia Sun, Heling Chen, Yirui Xie, Junwei Su, Ying Huang, Lijun Xu, Michael Yin, Qihui Zhou, Biao Zhu
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...
2017: Mediators of Inflammation
Patrick G Hogan
A cornerstone of the adaptive immune response is the T cell receptor (TcR)-calcium-calcineurin signalling pathway leading to T cell activation. The 'nuclear factor of activated T cells' proteins NFAT1, NFAT2, and NFAT4 are transcription factors that promote expression of a panel of genes required for activation. It has become apparent that these same NFAT transcription factors underlie an alternative transcriptional program in T cells that serves to limit the immune response. This duality in NFAT transcriptional functions raises the possibility that NFAT transcriptional complexes could be targeted therapeutically to alter the relative strength of the effector and alternative transcriptional programs, thereby modulating immune responses...
January 28, 2017: Cell Calcium
Yao-Te Hsieh, Poonam Aggarwal, David Cirelli, Ling Gu, Teresa Surowy, Ned M Mozier
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action (MOA) of several therapeutic antibody drugs and evaluation in ADCC bioassays is important in antibody drug development and maintenance. Three types of effector cells now routinely used in bioassay evaluation of ADCC are natural killer cells from human donors (FcγRIIIA+primary NK), FcγRIIIA engineered NK-92 cells and FcγRIIIA/NFAT-RE/luc2 engineered Jurkat T cells. Engineered effector cells were developed to address need for improved precision and accuracy of classic NK cell ADCC bioassays...
February 2017: Journal of Immunological Methods
Tingting Luo, Hongrui Liu, Wei Feng, Di Liu, Juan Du, Jing Sun, Wei Wang, Xiuchun Han, Jie Guo, Norio Amizuka, Xianqi Li, Minqi Li
OBJECTIVES: The purpose of this study was to investigate effects of adipocytes on osteoclast adhesion-related molecules. MATERIALS AND METHODS: ST2 cells, a cloned stromal cell line from mouse bone marrow, able to differentiate into adipocytes, were cultured in serum-free α-MEM which was then collected to be used as adipocyte-conditioned medium (ADIPO CM). RAW264.7 cells were cultured in ADIPO CM in the presence of RANKL, and bone marrow-derived macrophages were cultured in ADIPO CM in the presence of RANKL and macrophage-colony stimulating factor to induce osteoclast differentiation...
November 21, 2016: Cell Proliferation
Emilia Pachulec, Vanessa Neitzke-Montinelli, João P B Viola
Nuclear factor of activated T cells (NFAT) 2 null mutant mice die in utero of cardiac failure, precluding analysis of the role of NFAT2 in lymphocyte responses. Only the NFAT2(-/-)/Rag-1(-/-) chimeric mice model gave insight into the role of NFAT2 transcription factor in T lymphocyte development, activation, and differentiation. As reports are mainly focused on the role of NFAT2 in CD4(+) T lymphocytes activation and differentiation, we decided to investigate NFAT2's impact on CD8(+) T lymphocyte responses...
2016: Frontiers in Immunology
Xing-Mei Yao, Yu-Jun Liu, Yun-Man Wang, Hao Wang, Bing-Bing Zhu, Yong-Ping Liang, Wei-Guo Yao, Hui Yu, Nian-Song Wang, Xue-Mei Zhang, Wen Peng
Diabetic nephropathy (DN) is one of the most important causes of end‑stage renal disease. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus, which possesses various pharmacological activities. AS‑IV prevents podocyte apoptosis and ameliorates renal injury in DN; however, few studies have focused on its effects on ion channels. The transient receptor potential channel 6 (TRPC6) is an important Ca2+‑permeable ion channel in podocytes, which is involved in high glucose (HG)-induced podocyte apoptosis...
June 2016: Molecular Medicine Reports
Gustavo J Martinez, Joyce K Hu, Renata M Pereira, Jordan S Crampton, Susan Togher, Nicholas Bild, Shane Crotty, Anjana Rao
Follicular CD4(+) Th (Tfh) cells provide B cell help in germinal center reactions that support class switching, somatic hypermutation, and the generation of high-affinity Abs. In this article, we show that deficiency in NFAT1 and NFAT2 in CD4(+) T cells leads to impaired germinal center reactions upon viral infection because of reduced Tfh cell differentiation and defective expression of proteins involved in T/B interactions and B cell help, including ICOS, PD-1, and SLAM family receptors. Genome-wide chromatin immunoprecipitation data suggest that NFAT proteins likely directly participate in regulation of genes important for Tfh cell differentiation and function...
March 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Qing Zhao, Li Wang, Jie Hu, Hui Liu
OBJECTIVE: To investigate the role of nuclear factor of activated T cells -2 (NFAT2) in release of high mobility protein box-1 (HMGB1) from human monocytic THP-1 cells in vitro. METHODS: The level of HMGB1 release from THP-1 cells in response to lipopolysaccharide (LPS) stimulation was examined by Western blotting and enzyme-linked immunosorbent assay (ELISA). The effect of LPS stimulation on NFAT2 and HMGB1 interaction in the cytoplasm was observed by immunoprecipitation assay...
January 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Joo-Young Im, Kang-Woo Lee, Kyoung-Jae Won, Bo-Kyung Kim, Hyun Seung Ban, Sung-Hoon Yoon, Young-Ju Lee, Young-Joo Kim, Kyung-Bin Song, Misun Won
DNA damage induced apoptosis suppressor (DDIAS), or human Noxin (hNoxin), is strongly expressed in lung cancers. DDIAS knockdown induced apoptosis in non-small cell lung carcinoma A549 cells in response to DNA damage, indicating DDIAS as a potential therapeutic target in lung cancer. To understand the transcriptional regulation of DDIAS, we determined the transcription start site, promoter region, and transcription factor. We found that DDIAS transcription begins at nucleotide 212 upstream of the DDIAS translation start site...
December 2015: Data in Brief
Chiharu Miyajima, Yuka Itoh, Yasumichi Inoue, Hidetoshi Hayashi
Tribbles 1 (TRB1), a member of the Tribbles family, is a pseudokinase that is conserved among species and implicated in various human diseases including leukemia, cardiovascular diseases, and metabolic disorders. However, the role of TRB1 in the immune response is not understood. To evaluate this role, we examined regulation of TRB1 expression and the function of TRB1 in interleukin-2 (IL-2) induction in Jurkat cells, a human acute T cell leukemia cell line. We found that TRB1 was strongly induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin in these cells...
2015: Biological & Pharmaceutical Bulletin
Yixuan Huang, Mengrou Ren, Ying Xiong, Tong Wang, Hongyu Chen, Xuming Deng, Jing Lu
Tubeimoside-1 (TBMS1) is one of the important components in Bolbostemma paniculatum (Maxim.) Franque. In the study, its immunosuppressive effects on murine T lymphocyte responses were evaluated in vitro and in vivo. The data showed that TBMS1 inhibited ConA-induced T lymphocyte proliferation, decreased the ratio of CD4(+)/CD8(+), suppressed IL-2, IFN-γ, IL-4 and IL-6 production and mRNA expression, down-regulate activation of NF-κB, NFAT2 and AP-1 signal transduction pathways in vitro. In addition, administration of TBMS1 significantly inhibited T cell-mediated DTH response in vivo...
2015: Immunopharmacology and Immunotoxicology
Ke Ke, Ali Muhammad Safder, Ok-Joo Sul, Jae-Hee Suh, Yeonsoo Joe, Hun-Taeg Chung, Hye-Seon Choi
BACKGROUND: Cilostazol has been reported to alleviate the metabolic syndrome induced by increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, which is also associated with osteoclast (OC) differentiation. We hypothesized that bone loss might be attenuated via an action on OC by cilostazol. METHODOLOGY AND PRINCIPAL FINDINGS: To test this idea, we investigated the effect of cilostazol on ovariectomy (OVX)-induced bone loss in mice and on OC differentiation in vitro, using μCT and tartrate-resistant acid phosphatase staining, respectively...
2015: PloS One
(no author information available yet)
Our backcover features immunofluorescent stainings of cytospins of Nfat1(-/-) Th cell cultures stained with anti-NFAT2 and DAPI. The image relates to the article by Dietz et al. (pp. 1377-1389) in which the authors show that a combined lack of NFAT1 and NFAT2 completely protects mice from experimental autoimmune encephalomyelitis (EAE) disease. Single deficiency of either NFAT1 or NFAT2 ameliorated the course of EAE. Therefore the authors state that blocking NFAT in toto may be an option for immunosuppressive therapy...
May 2015: European Journal of Immunology
X Yuan, J Cao, T Liu, Y-P Li, F Scannapieco, X He, M J Oursler, X Zhang, J Vacher, C Li, D Olson, S Yang
Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre...
December 2015: Cell Death and Differentiation
Jiayou Tang, Xiaohui Zhou, Jie Liu, Qingshu Meng, Yang Han, Zhulin Wang, Huimin Fan, Zhongmin Liu
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...
October 2015: International Immunopharmacology
C Di Nisio, V L Zizzari, S Zara, M Falconi, G Teti, G Tetè, A Nori, V Zavaglia, A Cataldi
Osteonecrosis of the jaw (ONJ) is a chronic complication affecting long-term bisphosphonate-treated subjects, recognized by non-healing exposed bone in the maxillofacial region. The pathophysiological mechanism underlying ONJ has not been fully elucidated. The aim of the present study was to investigate the role of RANK/RANKL/OPG signaling pathway and, in parallel, to evaluate angiogenic and matrix mineralization processes in jaw bone necrotic samples obtained from bisphosphonate-treated subjects with established ONJ...
2015: European Journal of Histochemistry: EJH
Ryota Nakazato, Takeshi Takarada, Shinsuke Ikeno, Saki Nakamura, Takaya Kutsukake, Eiichi Hinoi, Yukio Yoneda
We have shown constitutive expression of the master regulator of osteoblastogenesis, runt-related transcription factor-2 (Runx2), by microglia cells outside bone. Here, we attempted to evaluate the pathological significance of Runx2 in microglial BV-2 cells exposed to ATP at a high concentration. Marked upregulation of Runx2 transcript and protein expression was seen in cells exposed to 1 mM ATP for a period longer than 30 min without inducing cytotoxicity. The Runx2 upregulation by ATP was prevented by extracellular and intracellular Ca(2+) chelators, while thapsigargin upregulated Runx2 expression alone without affecting the upregulation by ATP...
October 2015: Journal of Cellular Physiology
B Ye, X Liu, X Li, H Kong, L Tian, Y Chen
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...
March 19, 2015: Cell Death & Disease
C Tran Quang, S Leboucher, D Passaro, L Fuhrmann, M Nourieh, A Vincent-Salomon, J Ghysdael
Nuclear factor of activated T cells 1 (NFAT1) expression has been associated with increased migratory/invasive properties of mammary tumor-derived cell lines in vitro. It is unknown, however, if NFAT activation actually occurs in breast cancer cases and whether the calcineurin/NFAT pathway is important to mammary tumorigenesis. Using a cohort of 321 diagnostic cases of the major subgroup of breast cancer, we found Cn/NFAT pathway activated in ER(-)PR(-)HER2(-) triple-negative breast cancer subtype, whereas its prevalence is less in other subgroups...
2015: Cell Death & Disease
Lena Dietz, Friederike Frommer, Anna-Lena Vogel, Martin Vaeth, Edgar Serfling, Ari Waisman, Mathias Buttmann, Friederike Berberich-Siebelt
EAE serves as an animal model for multiple sclerosis and is initiated by autoreactive T cells that infiltrate the CNS. Recognition of myelin-associated Ags within the CNS leads to activation of the transcription factor family NFAT. Here, we demonstrate an essential role for NFAT in disease induction, as the combined lack of NFAT1 (NFATc2) and NFAT2 (NFATc1) completely protected mice. Single deficiency of either NFAT1 or NFAT2 ameliorated the course of EAE, and NFAT2 ablation resulted in an obstructed proinflammatory reaction...
May 2015: European Journal of Immunology
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