Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) are endothelial surface molecules that play a role for leukocyte recruitment to sites of inflammation, e.g., during contact hypersensitivity. We studied the effects of sensitizing agents (2,4-dinitro-benzenesulfonic acid, metal salt haptens) and chemically related substances on endothelial adhesion molecule expression. Using flow cytometry and an enzyme-linked immunosorbent assay, NiCl2 and, to a lesser extent, CoCl2 were found to up-regulate ICAM-1, VCAM-1, and ELAM-1 expression on cultured human umbilical vein endothelium whereas the other substances tested showed no effects. Induction of adhesion molecules by NiCl2 required de novo mRNA and protein synthesis. Up-regulation could be blocked by kinase inhibitor H-7 but not staurosporine, suggesting involvement of phosphorylation events independent of protein kinase C activation. Concomitant application of NiCl2 and neutralizing antibodies to IL-1 did not block up-regulation by the hapten demonstrating that the latter did not act via an IL-1-dependent autocrine mechanism. Regarding ELAM-1 induction, pre-treatment for 24 h with NiCl2 produced hyporesponsiveness to IL-1 and TNF-alpha upon restimulation, suggesting that NiCl2 and these cytokines may partially share a common pathway of activation. In addition, analysis of cultured foreskin specimens revealed that NiCl2 may induce up-regulation of ELAM-1 on microvascular endothelium in vivo. Our data demonstrate that both Ni++ and Co++ to which simultaneous contact sensitivity is frequently observed have the ability to directly up-regulate endothelial adhesion molecules. This shared property may represent an adjuvant mechanism that promotes sensitization and elicitation events in contact hypersensitivity to these haptens.
 ...
PMID:Nickel chloride and cobalt chloride, two common contact sensitizers, directly induce expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells. 768 25

The properties of a polymer surface affect the cellular functions and morphology of cells in contact with the polymer. In this paper, we will demonstrate the effects of surface modification of materials on various neutrophil markers of activation. The sulfonation of a polystyrene surface caused increases in its negative charge and hydrophilicity. The sulfonation did not affect the number of adhered neutrophils, but the shape of the neutrophils adhered on the material was different; a round shape on highly sulfonated polystyrene and a spread shape on weakly sulfonated or non-sulfonated polystyrene. Expression of the adhesion molecule, CD11b, on neutrophils was also affected by the properties of the polymer surface. CD11b was expressed in neutrophils adhered on polystyrene and the expression decreased with increasing sulfonation of the surface. The expression of CD11b on the neutrophils on highly sulfonated polystyrene was the same as that on non-adhered neutrophils. In contrast, the expression of CD11a was not affected by the properties of the material surface. The F-actin content of activated neutrophils and the production of active oxygen groups detected by means of luminol-dependent chemiluminescence were also dependent on the sulfo-group content of the material surface. Finally, the translocation of protein kinase C (PKC) was determined in neutrophils adhered to these materials. Compared to non-adhered cells, the ratio of membrane bound to cytosolic PKC increased in adhered cells, but the increase was suppressed by sulfonation of the material surface. These data suggest that activation of neutrophils on polystyrene is suppressed by surface modification with increasing negative charge and/or hydrophilicity.
 ...
PMID:Effects of surface modification of materials on human neutrophil activation. 772 29

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a widely distributed cell adhesion molecule present on monocytes, macrophages, and monocytic cell lines. Treatment of the promonocytic cell line U-937 with TGF-beta 1 induces homotypic cellular aggregations, simultaneous with an increase in surface expression and specific transcripts of PECAM-1. The TGF-beta-induced cell adhesion phenomena are not dependent on LFA-1, intercellular adhesion molecule-1 (ICAM-1), very late Ag-4 (VLA-4), or very late Ag-5 (VLA-5). However, the phenomena seem to be directly mediated by PECAM-1 because 1) it is inhibited by the addition of Abs or an antisense oligonucleotide specific for PECAM-1; and 2) TGF-beta 1-treated U-937 cells bind to PECAM-1-expressing mouse transfectant fibroblasts, but not to mock transfectants. In addition, this aggregation phenomena are divalent cation-dependent and requires the integrity of the cytoskeleton. Analysis of the intracellular signaling pathways indicates that TGF-beta 1 induces protein kinase C activity, as well as PECAM-1 phosphorylation and association with cytoskeletal components. Furthermore, in this model, an autocrine mechanism for releasing the bioactive form of TGF-beta 1 operates, allowing PECAM-1 activation. These results provide evidence that TGF-beta 1 regulates PECAM-1 function by increasing the expression and activating the adhesion of PECAM-1 in monocytic cells. These two mechanisms seem to be necessary for adhesion because independent inhibition of either expression or activation of PECAM-1 leads to abrogation of cellular aggregation.
 ...
PMID:Functional regulation of platelet/endothelial cell adhesion molecule-1 by TGF-beta 1 in promonocytic U-937 cells. 793 Jun 23

Incubation of the human renal carcinoma cell line CaKi-1 with tumour necrosis factor alpha (TNF alpha) or the phorbol ester phorbol-12-myristate 13 acetate (PMA) strongly enhanced the immunocytochemical staining of the intercellular adhesion molecule ICAM-1, in a non-linear manner. Since PMA is capable of activating Ca2+/phospholipid-dependent protein kinase C (PKC), we investigated the role of this kinase during TNF alpha signal transduction. Calcium ionophore A23187 significantly enhanced PMA, but not TNF alpha-induced ICAM-1 staining. The PKC inhibitors H7, staurosporine and sphingosine abrogated the action of PMA, while TNF alpha was unaffected. Simultaneous incubation with TNF alpha and PMA resulted in maximal ICAM-1 staining significantly above values obtained when cultures were treated with either agent alone. Finally, chronic PMA treatment with subsequent TNF alpha stimulation enhanced ICAM-1 staining above values from cultures where TNF alpha was omitted. Our findings suggest that the immunocytochemical staining of ICAM-1 in CaKi-1 cells can be induced by TNF alpha through mainly PKC-independent mechanisms or by PMA through PKC-dependent mechanisms. The two agents may work synergistically in this respect.
 ...
PMID:Comparison of the effects of tumour necrosis factor alpha stimulation and phorbol ester treatment on the immunocytochemical staining of intercellular adhesion molecule 1 in human renal carcinoma cell cultures. 809 20

We have previously shown that minimally oxidized LDL (MM-LDL) activated endothelial cells to increase their interaction with monocytes but not neutrophils, inducing monocyte but not neutrophil binding and synthesis of monocyte chemotactic protein-1 and monocyte colony-stimulating factor (M-CSF). In the present studies we have examined the signaling pathways by which this monocyte-specific response is induced. Both induction of monocyte binding and mRNA levels for M-CSF by MM-LDL were not inhibited in protein kinase C-depleted endothelial cells. A number of our studies indicate that cAMP is the second messenger for the effects of MM-LDL cited above. Incubation of endothelial cells with MM-LDL caused a 173% increase in intracellular cAMP levels. Agents which increased cAMP levels, including cholera toxin, pertussis toxin, dibutyryl cAMP, and isoproterenol mimicked the actions of MM-LDL. Agents which elevated cAMP were also shown to activate NF kappa B, suggesting a role for this transcription factor in activation of monocyte-endothelial interactions. Although endothelial leukocyte adhesion molecule (ELAM) mRNA synthesis can be regulated by NF kappa B, ELAM was not expressed and ELAM mRNA was only slightly elevated in response to MM-LDL. We present evidence that induction of neutrophil binding by LPS is actually suppressed by agents that elevated cAMP levels.
 ...
PMID:Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. 839 92

Bistratene A (BisA) induced growth arrest in G2/M in HL60 cells. In addition, BisA-treated cells (50 nM for 48 h) became adherent and expressed the adhesion molecule CD11c, but did not express the monocyte enzyme alpha-napthyl acetate esterase or phagocytose complement coated yeasts. BisA activated protein kinase C (PKC)-delta and induced translocation of PKC-delta to the nucleus. This suggests that activation of PKC-delta can induce growth arrest and cell adhesion, but is insufficient to mediate full differentiation of HL60 cells. BisA has potential as a new probe for determining the function of PKC isoenzymes, specifically PKC-delta.
 ...
PMID:The polyether bistratene A activates protein kinase C-delta and induces growth arrest in HL60 cells. 865 26

Studies have shown that, among lipoxygenase metabolites examined, 15(S)-hydroperoxy-5,8,11,13-eicosa-tetraenoic acid (15[S]-HPETE), at micromolar concentrations, selectively causes injury to cultured endothelial cells. We investigated whether physiologically relevant concentrations of lipoxygenase metabolites affected the expression of cell adhesion molecules (CAMs) involved in the adhesion of leukocytes and/or the accumulation of leukocytes in the vascular endothelium, these being the initial events in endothelial cell injury. Among lipoxygenase metabolites, 15(S)-HPETE and 12(S)-HETE, at nanomolar concentrations, induced surface expression of a subset of cell adhesion molecules (CAM), ICAM-1, ELAM-1, and VCAM-1, in human umbilical vein endothelial cells (HUVEC), which is associated with an increased binding activity of the transcription factor, NF-kappa B, to the consensus motif common to the CAM genes in the HUVEC nuclear extracts. Furthermore, 15(S)-HPETE (1 nM) caused a threefold increase in the rate of transendothelial migration of vitamin D3-differentiated HL-60 monocyte-like cells and showed a thirtyfold increase in the phosphorylation of PECAM-1, an adhesion molecule involved in endothelial cell-cell adhesion. Both an antibody to PECAM-1 and the protein kinase C inhibitor, GF 109203X, reduced 15(S)-HPETE-induced transmigration of monocyte-like HL-60 cells by approximately 75% and 85%, respectively. Treatment of HUVEC with a phosphatase inhibitor, calyculin A, augmented both the phosphorylation of PECAM-1 and transmigration of monocyte-like HL-60 cells induced by 15(S)-HPETE. Our results show that 15(S)-HPETE, at physiological concentrations, induced activation of protein kinase C in HUVEC and leads to the phosphorylation of PECAM-1, thus facilitating the migration of monocyte-like HL-60 cells across the endothelial cell monolayer. It is suggested that phosphorylation/dephosphorylation events in PECAM-1 are important in regulating the trafficking of monocytes across the endothelial cell monolayer.
 ...
PMID:Lipoxygenase metabolites induced expression of adhesion molecules and transendothelial migration of monocyte-like HL-60 cells is linked to protein kinase C activation. 865 2

Ligation of T-cell receptor (TCR) causes mature T cells to proliferate or, on re-exposure to antigen, can cause them to die by activation-induced cell death (AICD). In proliferative responses, costimulatory and adhesive interactions are required and activation of protein kinase C (PKC) has been shown to be essential. Whether or not interactions involving costimulatory signals and PKC have a role in facilitating AICD remains unclear. Here we have examined the role of CD28/B7 and leucocyte function associated antigen-1 (LFA-1)/intracellular adhesion molecule (ICAM) mediated interactions in AICD triggered by staphylococcal enterotoxin B (SEB) in murine lymph node T cells. We show that, after a primary proliferative response to SEB, LFA-1/ICAM-2 adhesive interactions can play a part in AICD following SEB rechallenge, while B7 and ICAM-1 mediated interactions are not essential for this process. In addition, using a highly selective PKC inhibitor, Ro31.8425, we show that PKC activation is essential for the regulation of AICD by SEB rechallenge.
 ...
PMID:Involvement of LFA-1/ICAM-2 adhesive interactions and PKC in activation-induced cell death following SEB rechallenge. 867 10

Airway smooth muscle plays a principal role in the pathogenesis of asthma. Primary cultures are being used to investigate airway myocyte proliferation and cellular pathways regulating contraction. Airway smooth muscle cells (SMC) modulate from a contractile to a noncontractile phenotype in culture, but no systematic study of the concomitant changes in expression of cytocontractile and cytoskeletal proteins has been reported. We measured temporal changes in protein marker expression of canine tracheal SMC in primary culture, using specific antibodies and cDNA probes. Immunoblot analysis revealed that when cells became proliferative after 5 days of culture, the content of smooth muscle myosin heavy chain (sm-MHC), calponin, sm-alpha-actin, and desmin diminished by > 75%; myosin light chain kinase, h-caldesmon, and beta-tropomyosin had also decreased significantly (P < 0.05). Northern blots revealed that mRNA levels for sm-MHC and sm-alpha-actin were also significantly reduced in proliferative SMC. Conversely, immunoblotting demonstrated the content of non-muscle myosin heavy chain, l-caldesmon, vimentin, alpha/beta-protein kinase C (PKC), and CD44 homing cellular adhesion molecule (HCAM) increased one- to sixfold as cells became proliferative. The content of sm-MHC and sm-alpha-actin protein increased after confluence, suggesting that cultured airway SMC are capable of phenotypic plasticity. Marker protein contents were also compared, by immunoblot assay, between SMC dissociated from trachealis or pulmonary arterial media. Cytocontractile protein content was higher in the trachea, which shortens faster than the pulmonary artery. The identification of these markers provides tools for assessing the phenotype of airway SMC in culture and the airways of asthmatic patients.
 ...
PMID:Markers of airway smooth muscle cell phenotype. 876 31

Growth factor-activated and cell adhesion-mediated signaling plays a crucial role in the development and differentiation of oligodendrocytes and astrocytes, the two macroglial cells of the CNS. Guided by the recent advances in the elucidation of intracellular signaling pathways, researchers have begun to investigate the mechanisms that regulate gliogenesis, glial cell differentiation and myelinogenesis. The progress made so far strongly implicates protein kinase C (PKC)- and protein kinase A (PKA)-mediated signaling in glial cell proliferation and differentiation. These pathways are also involved in the morphogenesis of astrocytes and in the myelin gene expression of oligodendrocytes. The cellular responses elicited by both PKC and PKA pathways in oligodendrocytes are developmentally controlled. The PKC pathway also seems to play a key role in phenotypic plasticity and regeneration of oligodendrocytes. Initial events of myelination requiring cell surface interactions may involve signaling via Fyn kinase which functionally associates with myelin-associated glycoprotein, an adhesion molecule implicated in myelinogenesis.
 ...
PMID:Signal transduction mechanisms in glial cells. 882 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>