scholarly journals Modulation of Dendritic Cell Apoptosis and CD8+Cytotoxicity by Histamine: Role of Protein Kinase C

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Julieta Alcain ◽  
Enrique Podaza ◽  
María Soledad Gori ◽  
Gabriela Salamone ◽  
Mónica Vermeulen
Keyword(s):  
T Lymphocytes ◽  
Inflammatory Responses ◽  
Cytolytic Activity ◽  
Cross Presentation ◽  
Kinase C ◽  
Histocompatibility Complex ◽  
First Time ◽  
G Protein Coupled ◽  
Pkc Activation

Dendritic cells (DC) are able to present extracellular antigens associated with the molecules of the major histocompatibility complex class I. In a previous work, we demonstrated that the histamine (HIS), acting through H1/H4 receptors, increases the cross-presentation of soluble ovalbumin by murine DC and can enhance the recruitment of specific CD8+T lymphocytes during the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying this enhancement. We showed that the cytotoxicity of specific CD8+lymphocytes is increased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosome acidification. It is known that HIS acts through G protein-coupled receptors. The H1/H4 receptors are associated with a Gqsubunit, which involves PKC signaling, a pathway related to the apoptotic process. Interestingly, we demonstrated for the first time that HIS prevents DC apoptosis induced by heat shock through the inhibition of caspase-3, a mechanism dependent on PKC activation, since it is reversed by its inhibition. By contrast, cytolytic activity of T lymphocytes induced by HIS-stimulated DC was independent of PKC pathway.

scholarly journals EnteroaggregativeEscherichia coliAdherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Erik J. Boll ◽  
Jorge Ayala-Lujan ◽  
Rose L. Szabady ◽  
Christopher Louissaint ◽  
Rachel Z. Smith ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Cell Receptor ◽  
Host Cell Receptor ◽  
Intestinal Infections ◽  
Elevated Expression ◽  
Intestinal Pathogen ◽  
Proinflammatory Role ◽  
First Time

ABSTRACTEnteroaggregativeEscherichia coli(EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen.IMPORTANCEEAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs—the principal adhesins of EAEC—in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.

Sustained muscle contraction induced by agonists, growth factors, and Ca2+ mediated by distinct PKC isozymes

2000 ◽  
Vol 279 (1) ◽  
pp. G201-G210 ◽  
Author(s):  
K. S. Murthy ◽  
J. R. Grider ◽  
J. F. Kuemmerle ◽  
G. M. Makhlouf
Keyword(s):  
Growth Factors ◽  
G Protein ◽  
Muscle Cells ◽  
Sustained Contraction ◽  
Calphostin C ◽  
Epidermal Growth ◽  
Pkc Isozymes ◽  
G Protein Coupled ◽  
Pkc Activation

The role of protein kinase C (PKC) in sustained contraction was examined in intestinal circular and longitudinal muscle cells. Initial contraction induced by agonists (CCK-8 and neuromedin C) was abolished by 1) inhibitors of Ca2+ mobilization (neomycin and dimethyleicosadienoic acid), 2) calmidazolium, and 3) myosin light chain (MLC) kinase (MLCK) inhibitor KT-5926. In contrast, sustained contraction was not affected by these inhibitors but was abolished by 1) the PKC inhibitors chelerythrine and calphostin C, 2) PKC-ε antibody, and 3) a pseudosubstrate PKC-ε inhibitor. GDPβS abolished both initial and sustained contraction, whereas a Gαq/11 antibody inhibited only initial contraction, implying that sustained contraction was dependent on activation of a distinct G protein. Sustained contraction induced by epidermal growth factor was inhibited by calphostin C, PKC-α,β,γ antibody, and a pseudosubstrate PKC-α inhibitor. Ca2+ (0.4 μM) induced an initial contraction in permeabilized muscle cells that was blocked by calmodulin and MLCK inhibitors and a sustained contraction that was blocked by calphostin C and a PKC-α,β,γ antibody. Thus initial contraction induced by Ca2+, agonists, and growth factors is mediated by MLCK, whereas sustained contraction is mediated by specific Ca2+-dependent and -independent PKC isozymes. G protein-coupled receptors are linked to PKC activation via distinct G proteins.

PDGF-induced mitogenic signaling is not mediated through protein kinase C and c-fos pathway in VSM cells

1993 ◽  
Vol 264 (1) ◽  
pp. C71-C79 ◽  
Author(s):  
R. V. Sharma ◽  
R. C. Bhalla
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
Thymidine Incorporation ◽  
Cytosolic Calcium ◽  
Platelet Derived Growth Factor ◽  
Kinase C ◽  
Pdgf Stimulation ◽  
Pkc Activation

This study examines the role of protein kinase C (PKC) in platelet-derived growth factor (PDGF)-induced vascular smooth muscle (VSM) cell proliferation and initial signaling events. A 24-h pretreatment of VSM cells with 200 nM phorbol 12-myristate 13-acetate (PMA) completely abolished immunologically reactive PKC activity. Depletion of PKC activity from VSM cells did not attenuate PDGF-stimulated [3H]thymidine incorporation compared with control cells. Similarly, acute activation of PKC by treatment with 200 nM PMA for 10 min had no effect on PDGF-mediated [3H]thymidine incorporation. Both PMA and PDGF increased c-fos induction to the same magnitude; however, treatment with PMA did not induce DNA synthesis in these cells. In PKC-depleted cells PDGF-mediated c-fos induction was reduced by 50-60%, while DNA synthesis in response to PDGF stimulation was not reduced. PKC depletion did not alter PDGF-stimulated increase in cytosolic calcium levels, 125I-PDGF binding, or receptor autophosphorylation. On the basis of these results, we conclude that PKC activation and c-fos induction do not play a significant role in PDGF-mediated mitogenesis in VSM cells.

scholarly journals Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms: role of NAD+/nicotinamide

2019 ◽  
Vol 116 (14) ◽  
pp. 2226-2238 ◽  
Author(s):  
Tetsuo Horimatsu ◽  
Andra L Blomkalns ◽  
Mourad Ogbi ◽  
Mary Moses ◽  
David Kim ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Aortic Aneurysms ◽  
Cell Infiltration ◽  
Protective Effects ◽  
Abdominal Aortic ◽  
G Protein Coupled

Abstract Aims Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation. Methods and results Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation. Conclusion Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.

Protein kinase C regulates endocytosis and recycling of E-cadherin

2002 ◽  
Vol 283 (2) ◽  
pp. C489-C499 ◽  
Author(s):  
Tam Luan Le ◽  
Shannon R. Joseph ◽  
Alpha S. Yap ◽  
Jennifer L. Stow
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Esters ◽  
Recycling Endosomes ◽  
Kinase C ◽  
Pkc Isozymes ◽  
Pkc Activation ◽  
Darby Canine Kidney ◽  
E Cadherin

E-cadherin is a major component of adherens junctions in epithelial cells. We showed previously that a pool of cell surface E-cadherin is constitutively internalized and recycled back to the surface. In the present study, we investigated the potential role of protein kinase C (PKC) in regulating the trafficking of surface E-cadherin in Madin-Darby canine kidney cells. Using surface biotinylation and immunofluorescence, we found that treatment of cells with phorbol esters increased the rate of endocytosis of E-cadherin, resulting in accumulation of E-cadherin in apically localized early or recycling endosomes. The recycling of E-cadherin back to the surface was also decreased in the presence of phorbol esters. Phorbol ester-induced endocytosis of E-cadherin was blocked by specific inhibitors, implicating novel PKC isozymes, such as PKC-ε in this pathway. PKC activation led to changes in the actin cytoskeleton facilitating E-cadherin endocytosis. Depolymerization of actin increased endocytosis of E-cadherin, whereas the PKC-induced uptake of E-cadherin was blocked by the actin stabilizer jasplakinolide. Our findings show that PKC regulates vital steps of E-cadherin trafficking, its endocytosis, and its recycling.

scholarly journals Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL-4 mutant cells.

1992 ◽  
Vol 175 (3) ◽  
pp. 843-846 ◽  
Author(s):  
R Glas ◽  
K Sturmhöfel ◽  
G J Hämmerling ◽  
K Kärre ◽  
H G Ljunggren
Keyword(s):  
Transfected Cells ◽  
Histocompatibility Complex ◽  
Tumorigenic Potential ◽  
Immunological Recognition ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
First Time ◽  
Mutant Cells

It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.

Phorbol 12,13-Diacetate-Induced Contraction of the Canine Basilar Artery: Role of Protein Kinase C

1991 ◽  
Vol 11 (1) ◽  
pp. 135-142 ◽  
Author(s):  
Makoto Sugawa ◽  
Tohru Koide ◽  
Shigetaka Naitoh ◽  
Michiaki Takato ◽  
Tohru Matsui ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Normal Medium ◽  
Kinase C ◽  
Prostaglandin F ◽  
Basilar Arteries ◽  
Canine Basilar Artery ◽  
Biochemical Mechanisms ◽  
Pkc Activation

The pharmacological and biochemical mechanisms of contractile responses to the protein kinase C (PKC) activator phorbol-12, 13-diacetate (PDA) were investigated in canine basilar arteries, In the normal medium, PDA elicited a strong, dose-related, and slow-developing sustained contraction, Among the constrictors examined, including serotonin, prostaglandin F2α and endothelin, only PDA yielded contractions in a 2 Ca2+ -free medium, In both media, the PDA-induced contractions were virtually inhibited by either staurosporine, H-7, or quinacrine, while neither neurotransmitter blockades nor R24571 (calmidazolium) exerted significant effects, In addition, it was shown that 8-bromocyclic GMP, but not 8-bromocyclic AMP, markedly curtailed the PDA-induced contractions, Biochemical analysis, furthermore, showed that PDA induced increased phosphorylations of 27- and 96-kDa and proteins other than the myosin light chain (MLC) 20-kDa protein, Thus, the present results open up a novel mechanism of sustained cerebral artery contractions, where PKC activation rather than Ca2+/calmodulin/MLC system plays a key role that is regulated both by phospholipase A 2 and by cyclic GMP.

scholarly journals Myeloid and Plasmacytoid Dendritic Cells and Cancer – New Insights

2019 ◽  
Vol 7 (19) ◽  
pp. 3324-3340 ◽  
Author(s):  
Maya Gulubova ◽  
Koni Vancho Ivanova ◽  
Mehmed Hadzhi ◽  
Dimitur Chonov ◽  
Maria Magdalena Ignatova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Mhc I ◽  
Cross Presentation ◽  
Adaptive Immune ◽  
Histocompatibility Complex ◽  
T Helpers

Dendritic cells (DCs) use effective mechanisms to combat antigens and to bring about adaptive immune responses through their ability to stimulate nӓive T cells. At present, four major cell types are categorised as DCs: Classical or conventional (cDCs), Plasmacytoid (pDCs), Langerhans cells (LCs), and monocyte-derived DCs (Mo-DCs). It was suggested that pDCs, CD1c+ DCs and CD141+ DCs in humans are equivalent to mouse pDCs, CD11b+ DCs and CD8α+ DCs, respectively. Human CD141+ DCs compared to mouse CD8α+ DCs have remarkable functional and transcriptomic similarities. Characteristic markers, transcription factors, toll-like receptors, T helpers (Th) polarisation, cytokines, etc. of DCs are discussed in this review. Major histocompatibility complex (MHC) I and II antigen presentation, cross-presentation and Th polarisation are defined, and the dual role of DCs in the tumour is discussed. Human DCs are the main immune cells that orchestrate the immune response in the tumour microenvironment.

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