T-cell signal transduction and the role of protein kinase C

Wilkinson, Sandra E.; Nixon, John

doi:10.1007/s000180050241

Cited by 26 publications

(18 citation statements)

References 139 publications

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“…significant increase in the total BALF cell counts on day 9, the first day of initiation of hypersensitivity in experimental group, which further increased (3.5 fold) on day 14, similar to the findings of Sakai et al [37]. PKC is one of the key enzymes that mediate inflammatory signals [38]. It represents a structurally homologous group of 12 isoforms which are divided into three sub-groups that differ in their cofactor requirements.…”

Section: Discussionsupporting

confidence: 85%

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Mishra¹,

Kulshrestha²,

Chhabra³

et al. 2014

OJRD

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Background and Objectives: Protein kinase C (PKC) activation plays an important role in activation of T-lymphocytes in asthma.Airway hypersensitivity is one of the main characteristic features of asthma, the mechanism of onset of which is not clearly understood. Therefore, the objective was to elucidate the role of PKC in etiopathogenesis of airway hypersensitivity in asthma. Methods: Male guinea pigs (n = 30) were sensitized with ovalbumin and day of initial allergen-specific immune response determined by intradermal test, airway hypersensitivity, BALF cytology and lung histopathology. Total PKC activity, PKC isoenzymes and phosphoinositides were assessed in airway smooth muscles (ASM) and peripheral blood lymphocytes. Results: Intradermal test revealed that day 9 was the earliest time of allergen-specific response and onset of airway hypersensitivity to ovalbumin. It was associated with significant increase in total and differential (lymphocytes and eosinophils) BALF counts and grade I peribronchiolar chronic lymphocytic inflammation in lung. On day 14, grade II infiltration of lymphocytes and eosinophils with onset ofstructural remodelingofproximal and distal airways was seen. Total PKC activity, expression of PKCα, PKCε and phosphoinositides increased significantly in ASM and lymphocytes on day 9 and were maximum on day 14. There was no change in PKC-τ expression. Conclusions: Activation of PKC, particularly PKCα and PKCε, mediated signal transduction pathway plays a critical role in lymphocyte infiltration and onset of airway hypersensitivity, airway remodeling and asthma pathophysiology. The present study is the first one on the mechanism of the etiopathogenesis of the disease, which shows a direct evidence of the role of PKC mediated pathway in the initiation and onset of airway hypersensitivity in ovalbumin sensitized guinea pig model.

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Section: Discussionsupporting

confidence: 85%

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Mishra¹,

Kulshrestha²,

Chhabra³

et al. 2014

OJRD

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“…The changes were further confirmed by histopathology of the lungs, e.g. there was a significant increase in the total BALF cell counts on day 9, the first day of initiation of hypersensitivity in experimental group, which further increased (3.5fold) on day 14, similar to the findings of Sakai et al 37 PKC is one of the key enzymes that mediate inflammatory signals. 38 It represents a structurally homologous group of 12 isoforms which are divided into three sub-groups that differ in their cofactor requirements.…”

Section: +supporting

confidence: 86%

Changes in Phosphoinositide Turnover in Airway Smooth Muscles and Blood Lymphocytes in Ova Sensitized Guinea Pig Model of Asthma

Mishra¹

2016

Pulm Res Respir Med Open J

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Citation ResearchPage 10 AbstRAct background and Objective: Bronchial asthma has been defined as a combination of reversible airway obstruction, increased airway responsiveness, and airway inflammation. Protein kinase C (PKC) is a primary group of enzymes mediating signal transduction for a wide variety of functions in many different cell types. Its activation has been implicated in various inflammatory diseases. Since PKC activity is regulated by the metabolic pool of phosphoinositides and their turnover. The involvement of these phospholipids in allergic inflammatory responses is, however, yet to be fully determined. To evaluate the changes in phosphoinositide turnover in guinea pig model of asthma and correlation with PKC activity. Methods: Male guinea pigs were sensitized with ovalbumin and day of initial allergen-specific immune response determined by intradermal test. Airway hyperresponsiveness was measured using a plethysmograph. Airway remodeling, content of mucin was assessed histochemically on lung sections, and bronchoalveolar lavaged fluid (BALF) cell composition. Total PKC activity, phosphoinositides were assessed in airway smooth muscles (ASM) and peripheral blood lymphocytes. Results: Compared with control mice, OVA-challenged mice led to enhanced recruitment of inflammatory cells in bronchoalveolar lavage fluid, increases in inflammation scores, collagen accumulation, bronchial wall thickness and inflammatory cytokines. Also, we examined total PKC activity is increased in ASM and lymphocytes isolated from both groups. The levels of phosphoinositide intermediates increased further in both ASM and lymphocyte in Ova-sensitized group as compared to control group. conclusion: Ova exposure aggravated airway inflammation, airway remodelling, activation of inflammatory cytokines, and increases PKC activity in OVA-sensitized and -challenged mice, correlated with total phosphoinositide intermediates increased further in both ASM and lymphocyte.

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“…Their functions rely on the complete activation and cytokine production, all of which have been targeted by anti-inflammatory or immunosuppressive agents [16,17]. In this study, we used Jurkat T cells as a cellular model to evaluate the anti-inflammatory effect of CucE and found that CucE could significantly inhibit the secretion of IL-2, TNF-α, and IFN-γ in activated Jurkat T cells.…”

Section: Discussionmentioning

confidence: 99%

“…The transcription of these cytokine genes is controlled by several critical signaling pathways including the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways [16,17]. These signaling cascades are involved in T cell activation and cytokine expression and have been investigated as targets for immunomodulatory or immunosuppressive agents [16,17]. Thus, it is of interest to explore the effect of CucE on the responses of T cells upon mitogen stimulation.…”

Section: Introductionmentioning

confidence: 99%

“…Upon activation, T cells produce a variety of cytokines including IL-2, TNF-α, and interferon (IFN)-γ, which not only affect the proliferation and functions of themselves but also act on other immune cells to modulate their responses [15,16]. The transcription of these cytokine genes is controlled by several critical signaling pathways including the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways [16,17]. These signaling cascades are involved in T cell activation and cytokine expression and have been investigated as targets for immunomodulatory or immunosuppressive agents [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling

Wang¹,

Li²,

Lin³

et al. 2015

ABBS

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Cucurbitacin E (CucE), a triterpenoid isolated from Cucurbitaceae plants, has been shown to possess an anti-inflammatory or immunosuppressive activity in vitro and in vivo, yet the underlying mechanism has been incompletely understood. The aim of the present study was to explore its effect on cytokine expression and the underlying mechanism in human Jurkat T cells as a cellular model. The results showed that CucE significantly inhibited the production of interleukin-2, tumor necrosis factor-α, and interferon-γ in culture medium of cells treated with phorbol 12,13-dibutyrate (PDB) plus ionomycin (Ion). Furthermore, the mRNA levels of these cytokines in activated Jurkat T cells were also decreased upon CucE treatment, suggesting a potential modulatory effect on the critical signaling pathways for cytokine expression, including nuclear factor-κB (NF-κB) or mitogen-activated protein kinases (MAPKs). In support of its effect on the NF-κB signaling pathway, CucE decreased the phosphorylation levels of inhibitor of κB (IκB) and NF-κB/p65 in PDB + Ion-stimulated cells. Further supporting this, the nuclear translocation of NF-κB/p65 was significantly suppressed in response to PDB plus Ion stimulation in the presence of CucE. The phosphorylation of p38MAPK, c-Jun N-terminal kinase (JNK), and Erk1/2, however, was not decreased or slightly increased at some time points by CucE treatment. Collectively, these data suggest that CucE may exhibit immunosuppressive effect by attenuating critical cytokine expression through down-regulating the NF-κB signaling pathway.

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T-cell signal transduction and the role of protein kinase C

Cited by 26 publications

References 139 publications

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Changes in Phosphoinositide Turnover in Airway Smooth Muscles and Blood Lymphocytes in Ova Sensitized Guinea Pig Model of Asthma

Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling

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T-cell signal transduction and the role of protein kinase C

Cited by 26 publications

References 139 publications

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Changes in Phosphoinositide Turnover in Airway Smooth Muscles and Blood Lymphocytes in Ova Sensitized Guinea Pig Model of Asthma

Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-&kappa;B signaling

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Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling