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Pkc theta

Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, Denise Soutar, Isabel Mérida
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation...
February 28, 2017: Immunology and Cell Biology
Jung-Ah Kang, Hyunwoo Choi, Taewoo Yang, Steve K Cho, Zee-Yong Park, Sung-Gyoo Park
PDK1 is essential for T cell receptor (TCR)-mediated activation of NF-κB, and PDK1-induced phosphorylation of PKCθ is important for TCR-induced NF-κB activation. However, inverse regulation of PDK1 by PKCθ during T cell activation has not been investigated. In this study, we found that PKCθ is involved in human PDK1 phosphorylation and that its kinase activity is crucial for human PDK1 phosphorylation. Mass spectrometry analysis of wild-type PKCθ or of kinase-inactive form of PKCθ revealed that PKCθ induced phosphorylation of human PDK1 at Ser-64...
January 2017: Molecules and Cells
Pei Wu, Yang Liu, Wei-Dan Jiang, Jun Jiang, Juan Zhao, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
The liver and intestine are susceptible to the oxidative damage which could result in several diseases. Choline deficiency induced oxidative damage in rat liver cells. Thus, this study aimed to investigate the potential molecular mechanisms responsible for choline deficiency-induced oxidative damage. Juvenile Jian carp were fed diets differing in choline content [165 (deficient group), 310, 607, 896, 1167 and 1820 mg/kg diet] respectively for 65 days. Oxidative damage, antioxidant enzyme activities and related gene expressions in the hepatopancreas and intestine were measured...
2017: PloS One
Maria Julia Marques
No abstract text is available yet for this article.
January 13, 2017: EBioMedicine
Mateus Feitosa Alves, Marcus Tullius Scotti, Luciana Scotti, Francisco Jaime Bezerra Mendonça Junior, José Maria Barbosa Filho, Sílvia Adelaide Linhares de Melo, Sócrates Golzio Dos Santos, Margareth de Fátima Formiga Melo Diniz
The genus Cissampelos comprises 21 species which have a wide global distribution and various pharmacological activities such as analgesic and antipyretic, anti-inflammatory, anti-allergic, bronchodilation, and immunomodulation among others. Several compounds, mainly alkaloids with differing biological activities have been isolated from this genus. We will highlight antipyretic activities, anti-inflammatory, antiallergic, bronchodilatory, and immunomodulatory activities. In addition, we applied ligand-based-virtual screening associated with structure-based-virtual screening of a small dataset of 63 secondary metabolites from the Cissampelos genus of an in-house data bank, in order to select compounds with potential anti-inflammatory activity...
December 27, 2016: Current Medicinal Chemistry
A Chen, W W Hu, X L Jiang, M Potegal, H Li
The roles of group I metabotropic glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) and mGluR5, in regulating synaptic plasticity and metaplasticity in the basolateral amygdala (BLA) remain unclear. The present study examined mGluR1- and mGluR5-mediated synaptic plasticity in the BLA and their respective signaling mechanisms. Bath application of the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG) (20 μM), directly suppressed basal fEPSPs (84.5 ± 6.3% of the baseline). The suppressive effect persisted for at least 30 min after washout; it was abolished by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) but was unaffected by the mGluR5 antagonist 2-methyl-6- (phenylethynyl)-pyridine (MPEP)...
December 28, 2016: Psychopharmacology
Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in TH2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble TH2 cells and produce the TH2 cytokines IL-5 and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct TH2 responses in patients with allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and might be necessary for ILC2s to instruct the TH2 response...
October 14, 2016: Journal of Allergy and Clinical Immunology
Jessica Byerly, Gwyneth Halstead-Nussloch, Koichi Ito, Igor Katsyv, Hanna Y Irie
BACKGROUND: The protein kinase C (PKC) family comprises distinct classes of proteins, many of which are implicated in diverse cellular functions. Protein tyrosine kinase C theta isoform (PRKCQ)/PKCθ, a member of the novel PKC family, may have a distinct isoform-specific role in breast cancer. PKCθ is preferentially expressed in triple-negative breast cancer (TNBC) compared to other breast tumor subtypes. We hypothesized that PRKCQ/PKCθ critically regulates growth and survival of a subset of TNBC cells...
2016: Breast Cancer Research: BCR
Cheng-Yu Chen, Chen-Ming Su, Chin-Jung Hsu, Chien-Chung Huang, Shih-Wei Wang, Shih-Chia Liu, Wei-Cheng Chen, Lih-Jyh Fuh, Chih-Hsin Tang
Angiogenesis is the formation of new capillaries from preexisting vasculature. The perpetuation of angiogenesis plays a critical role in the pathogenesis of various disease states including rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61 or CCN1) is an important proinflammatory cytokine in RA. Here, we investigated the role of CCN1 in angiogenesis associated with vascular endothelial growth factor (VEGF) production and osteoblasts. We found higher expression of CCN1 and VEGF in synovial fluid from RA patients compared with healthy controls...
January 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Christa Pfeifhofer-Obermair, Karin Albrecht-Schgoer, Sebastian Peer, Manfred Nairz, Kerstin Siegmund, Victoria Klepsch, David Haschka, Nikolaus Thuille, Natascha Hermann-Kleiter, Thomas Gruber, Günter Weiss, Gottfried Baier
BACKGROUND: The serine/threonine protein kinase C (PKC) theta has been firmly implicated in T cell-mediated immunity. Because its role in macrophages has remained undefined, we employed PKCtheta-deficient (PKCtheta (-/-)) mice in order to investigate if PKCtheta plays a role in macrophage-mediated immune responses during bacterial infections. RESULTS: Our results demonstrate that PKCtheta plays an important role in host defense against the Gram-negative, intracellular bacterium Salmonella typhimurium, as reflected both by markedly decreased survival and a significantly enhanced number of bacteria in spleen and liver of PKCtheta (-/-) mice, when compared to wild-type mice...
July 28, 2016: Cell Communication and Signaling: CCS
Purushotham Kkrishnappa, Eu Jhin Loh, Ibtisam Binti Mohamad, Mahadevan Deva Tata, Meenakshi Akhilesh, Kandasami Palayan
PURPOSE: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia. MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Deebika Balu, John R Larson, Jennifer V Schmidt, David Wirtshafter, Aleksey Yevtodiyenko, John P Leonard
Activity-dependent plasticity in NMDA receptor-containing synapses can be regulated by phosphorylation of serines and tyrosines in the C-terminal domain of the receptor subunits by various kinases. We have previously identified S1291/S1312 as important sites for PKC phosphorylation; while Y1292/Y1312 are the sites indirectly phosphorylated by PKC via Src kinase. In the oocyte expression system, mutation of those Serine sites to Alanine (that cannot be phosphorylated) in the GluN2A subunit, resulted in a decreased PKC stimulated current enhancement through the receptors compared to wild-type NMDA receptors...
September 1, 2016: Brain Research
Jasmine Li, Kristine Hardy, Chan Phetsouphanh, Wen Juan Tu, Elissa L Sutcliffe, Robert McCuaig, Christopher R Sutton, Anjum Zafar, C Mee Ling Munier, John J Zaunders, Yin Xu, Angelo Theodoratos, Abel Tan, Pek Siew Lim, Tobias Knaute, Antonia Masch, Johannes Zerweck, Vedran Brezar, Peter J Milburn, Jenny Dunn, Marco G Casarotto, Stephen J Turner, Nabila Seddiki, Anthony D Kelleher, Sudha Rao
Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation...
June 15, 2016: Journal of Cell Science
Izabela Michalczyk, Monika Toporkiewicz, Patrycja M Dubielecka, Anna Chorzalska, Aleksander F Sikorski
INTRODUCTION: During studies on chemotherapy-induced apoptosis in lymphoid cells, we noted that aggregation of spectrin occurred early in apoptosis, i.e. before activation of initiator caspase(s) and prior to exposure of phosphatidylserine (PS). We also found that protein kinase C theta (PKC-θ) co-localized with spectrin in these aggregates. Our previously published studies indicated that in formation of early apoptotic spectrin aggregates, either PKC-θ or other apoptosis-related proteins are involved...
2016: Folia Histochemica et Cytobiologica
Mao Mao, Yanning Qian, Jie Sun
To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner...
April 2016: Inflammation
Jin Kawata, Rui Yamaguchi, Takatoshi Yamamoto, Yasuji Ishimaru, Arisa Sakamoto, Manabu Aoki, Masafumi Kitano, Misako Umehashi, Eiji Hirose, Yasuo Yamaguchi
OBJECTIVE: Neutrophils have an important role in the rapid innate immune response, and the release or active secretion of elastase from neutrophils is linked to various inflammatory responses. Purpose of this study was to determine how the human neutrophil elastase affects the interleukin-10 (IL-10) response in peripheral blood mononuclear cells (PBMC). MATERIALS AND METHODS: In this prospective study, changes in IL-10 messenger RNA (mRNA) and protein expression levels in monocytes derived from human PBMCs were investigated after stimulation with human neutrophil elastase (HNE)...
2016: Cell Journal
Rouba Hage-Sleiman, Asmaa B Hamze, Aimée F El-Hed, Randa Attieh, Lina Kozhaya, Sarah Kabbani, Ghassan Dbaibo
Protein kinase C theta (PKCθ) is a novel, calcium-independent member of the PKC family of kinases that was identified as a central player in T cell signaling and proliferation. Upon T cell activation by antigen-presenting cells, PKCθ gets phosphorylated and activated prior to its translocation to the immunological synapse where it couples with downstream effectors. PKCθ may be regulated by ceramide, a crucial sphingolipid that is known to promote differentiation, growth arrest, and apoptosis. To further investigate the mechanism, we stimulated human Jurkat T cells with either PMA or anti-CD3/anti-CD28 antibodies following induction of ceramide accumulation by adding exogenous ceramide, bacterial sphingomyelinase, or Fas ligation...
August 2016: Immunologic Research
Nachimuthu Maithilikarpagaselvi, Magadi Gopalakrishna Sridhar, Rathinam Palamalai Swaminathan, Bobby Zachariah
Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats...
January 25, 2016: Chemico-biological Interactions
Robert Duncan McCuaig, Jennifer Dunn, Jasmine Li, Antonia Masch, Tobias Knaute, Mike Schutkowski, Johannes Zerweck, Sudha Rao
Alternative splicing of nuclear pre-mRNA is essential for generating protein diversity and regulating gene expression. While many immunologically relevant genes undergo alternative splicing, the role of regulated splicing in T cell immune responses is largely unexplored, and the signaling pathways and splicing factors that regulate alternative splicing in T cells are poorly defined. Here, we show using a combination of Jurkat T cells, human primary T cells, and ex vivo naïve and effector virus-specific T cells isolated after influenza A virus infection that SC35 phosphorylation is induced in response to stimulatory signals...
2015: Frontiers in Immunology
Vedran Brezar, Wen Juan Tu, Nabila Seddiki
One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/off of robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-θ) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells...
2015: Frontiers in Immunology
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