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NFAT2 cytokine

Muhammad S Alam, Matthias M Gaida, Subrata Debnath, Harichandra D Tagad, Lisa M Miller Jenkins, Ettore Appella, M Jubayer Rahman, Jonathan D Ashwell
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...
January 2018: PLoS Biology
Osamu Kaminuma, Noriko Kitamura, Yasumasa Nishito, Soichi Nemoto, Hideki Tatsumi, Akio Mori, Takachika Hiroi
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...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Bilin Nie, Cuicui Liu, Xiaohui Bai, Xiaodi Chen, Shaoyong Wu, Subo Zhang, Zhuxi Huang, Manxiu Xie, Ting Xu, Wenjun Xin, Weian Zeng, Handong Ouyang
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...
February 2018: Brain, Behavior, and Immunity
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
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
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
Shuang Guan, Baochen Fang, Bocui Song, Ying Xiong, Jing Lu
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(+)...
August 2014: Immunopharmacology and Immunotoxicology
Mari-Pau Mena, Izabela Papiewska-Pajak, Patrycja Przygodzka, Anna Kozaczuk, Joanna Boncela, Czeslaw S Cierniewski
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...
June 10, 2014: Experimental Cell Research
Ying Xiong, Shuang Zhang, Jing Lu, Shicheng Sun, Bocui Song, Linli Xu, Zhenguo Yang, Shuang Guan
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...
June 2013: International Immunopharmacology
Osamu Kaminuma, Noriko Kitamura, Akio Mori, Hideki Tatsumi, Soichi Nemoto, Takachika Hiroi
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...
2012: International Archives of Allergy and Immunology
Rizgar A Mageed, Soizic Garaud, Taher E Taher, Kaushal Parikh, Jacques-Olivier Pers, Christophe Jamin, Yves Renaudineau, Pierre Youinou
CD5(+) B lymphocytes have distinct functional properties compared with B lymphocytes that lack CD5. However, it remains unclear if and how the CD5 molecule modulates B lymphocyte biology and responses. Our recent studies have revealed that CD5 promotes constitutive activation of multiple signaling pathways including extracellular signal-regulated kinases (ERK1/2), phosphatidylinositol 3-kinase (PI-3K)/mammalian target of rapamycin (mTOR) and calcineurin-NFAT signaling pathways. Further, changes in cytokine production including the production of IL-10 are related to the activation of the transcription factors NFAT2 and STAT3...
September 2012: Autoimmunity Reviews
Soizic Garaud, Ahsen Morva, Sébastien Lemoine, Sophie Hillion, Anne Bordron, Jacques-Olivier Pers, Christian Berthou, Rizgar A Mageed, Yves Renaudineau, Pierre Youinou
B lymphocytes from chronic lymphocytic leukemia (CLL) display some CD5 transcripts for CD5 containing the known exon 1 (E1A) and other CD5 transcripts containing the new exon 1 (E1B). These malignant B cells, as well as B cell lines transfected with cDNA for E1A-cd5 or with cDNA for E1B-cd5 produce IL-10, raising the possibility that CD5 participates in the secretion of IL-10. We identified transcription factors involved in this production in CD5(+) B lymphocytes from CLL patients and in E1A-cd5-transfected or E1B-cd5-transfected Jok cells...
April 15, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
Ayse B Celil Aydemir, Hiroshi Minematsu, Thomas R Gardner, Kyung Ok Kim, Jae Mok Ahn, Francis Young-In Lee
Mechanical loading such as interstitial fluid shear stress and tensile strain stimulates bone cells, which respond by changing bone mass and structure to maintain optimal skeletal architecture. Bone cells also adapt to bone implants and altered mechanical loading. Osseous integration between host bone and implants is a prerequisite for the stability of implants. Fluctuating fluid pressure and interfacial strains occur between bone cells and implants due to mechanical loading during walking and other daily activities...
January 2010: Bone
Troy R Torgerson, Anna Genin, Chunxia Chen, Mingce Zhang, Bin Zhou, Stephanie Añover-Sombke, M Barton Frank, Igor Dozmorov, Elizabeth Ocheltree, Petri Kulmala, Michael Centola, Hans D Ochs, Andrew D Wells, Randy Q Cron
The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4(+)CD25(+) regulatory T cells (T(REG)), which play a key role in maintaining self-tolerance. Functionally, FOXP3 is capable of repressing transcription of cytokine genes regulated by NFAT. Various mechanisms have been proposed by which FOXP3 mediates these effects. Using novel cell lines that inducibly express either wild-type or mutant FOXP3, we have identified NFAT2 as an early target of FOXP3-mediated transcriptional repression...
July 15, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
Yasuhiro Yamanaka, Wahid Abu-Amer, Dominica Foglia, Jesse Otero, John C Clohisy, Yousef Abu-Amer
Particle-induced periprosthetic osteolysis is the major cause for orthopedic implant failure. This failure is mediated mainly by the action of osteoclasts, the principal cells responsible for bone resorption and osteolysis. Therapeutic interventions to alleviate osteolysis have been focused on understanding and targeting mechanisms of osteoclastogenesis. The nuclear transcription factor NFAT is an essential terminal differentiation factor of osteoclastogenesis. This transcription factor is known to cooperate with c-jun/AP-1 in mediating RANKL-induced osteoclastogenesis...
December 2008: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Russell Quapp, Norman Madsen, Lisa Cameron
Chemoattractant-receptor homologous molecule expressed on Th2 cells (CRTh2) is a receptor for prostaglandin (PG)D2, a lipid mediator involved in allergic inflammation. CRTh2 is expressed by Th2 cells, eosinophils and basophils and PDG(2)-CRTh2 signaling induces calcium mobilization, cell migration and expression of the Th2 cytokines IL-4, IL-5, and IL-13. Despite the role of CRTh2 in allergic inflammation, transcriptional regulation of this gene has not been studied. Here, we demonstrated that a reporter construct of the CRTh2 promoter was induced following T cell stimulation...
November 30, 2007: Biochemical and Biophysical Research Communications
Martin K Andersson, Pernilla Lundberg, Acke Ohlin, Mark J Perry, Anita Lie, André Stark, Ulf H Lerner
Aseptic loosening of a joint prosthesis is associated with remodelling of bone tissue in the vicinity of the prosthesis. In the present study, we investigated the effects of synovial fluid (SF) from patients with a loose prosthetic component and periprosthetic osteolysis on osteoclast and osteoblast activities in vitro and made comparisons with the effects of SF from patients with osteoarthritis (OA). Bone resorption was assessed by the release of calcium 45 (45Ca) from cultured calvariae. The mRNA expression in calvarial bones of molecules known to be involved in osteoclast and osteoblast differentiation was assessed using semi-quantitative reverse transcription-polymerase chain reaction (PCR) and real-time PCR...
2007: Arthritis Research & Therapy
Zheng-Yu Wang, Saritha Kusam, Veerendra Munugalavadla, Reuben Kapur, Randy R Brutkiewicz, Alexander L Dent
NKT cells are unique in that they can produce high levels of both Th1 and Th2 cytokines, yet little is known about how NKT cells control the transcription of Th2 cytokines. The expression of IL-4 by NKT cells is independent of the Th2-associated transcription factor Stat6. We have found that Stat6 is critical for the expression of IL-5, IL-10, and IL-13 by NKT cells. However, the Th2 cell-associated transcription factor GATA-3, normally induced by Stat6 activation, is expressed at low levels in NKT cells. CD4+ NKT cells are highly enriched for Th2 cytokine expression compared with CD4- NKT cells, and we searched for transcription factors that are up-regulated in CD4+ NKT cells that could control Th2 cytokine expression...
January 15, 2006: Journal of Immunology: Official Journal of the American Association of Immunologists
Py Palmqvist, Pernilla Lundberg, Emma Persson, Anders Johansson, Inger Lundgren, Anita Lie, H Herschel Conaway, Ulf H Lerner
Interleukin (IL)-4 and IL-13 are cytokines that inhibit bone resorption. Data showing an inhibitory effect of IL-4 and IL-13 on RANK mRNA in mouse calvariae were first reported at the 22nd American Society for Bone and Mineral Research Meeting (Lerner, U.H., and Conaway, H. H. 2000) J. Bone Min. Res. 15, Suppl. 1, Abstr. SU 230). In the present study, release of 45Ca from cultured mouse calvarial bones stimulated by different cytokines, peptides, and steroid hormones was inhibited by IL-4 and IL-13. IL-4 and IL-13 decreased receptor activator of nuclear factor-kappaB ligand (RANKL) and RANK mRNA and increased osteoprotegerin (OPG) mRNA in calvariae...
February 3, 2006: Journal of Biological Chemistry
Winifred Huang, Hans D Ochs, Bo Dupont, Yatin M Vyas
Effector functions mediated by NK cells involve cytotoxicity and transcription-dependent production and release of cytokines and chemokines. Although the JAK/STAT pathway mediates lymphokine-induced transcriptional regulation in NK cells, very little is known about transcriptional regulation induced during cell-cell contact. We demonstrate that the Wiskott-Aldrich syndrome protein (WASp) is an important component for integration of signals leading to nuclear translocation of NFAT2 and NF-kappaB (RelA) during cell-cell contact and NKp46-dependent signaling...
March 1, 2005: Journal of Immunology: Official Journal of the American Association of Immunologists
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