Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration

Ng, Chin Theng; Fong, Lai Yen; Sulaiman, Mohd Roslan; Moklas, Mohamad Aris Mohd; Yong, Yoke Keong; Hakim, Muhammad Nazrul; Ahmad, Zubair

doi:10.1089/jir.2014.0188

Cited by 42 publications

(26 citation statements)

References 45 publications

(12 reference statements)

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“…In this study, the highest aortic endothelial cell permeability was observed at 10 ng/ml of TNF-α and 24 h of incubation period. Our result is in agreement with cytokineinduced increased permeability in human umbilical vein endothelial cells (McKenzie & Ridley, 2007;Ng et al, 2015). However, we found that TNF-α exerted a direct toxic effect on HAEC after incubated for 24 h. This is consistent with previous studies that demonstrated the apoptotic effect of TNF-α in endothelial cells (Aveleira et al, 2010;Petrache et al, 2001).…”

Section: Discussionsupporting

confidence: 93%

Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells

Fong

Zakaria

et al. 2015

Phytother. Res.

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The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC). TNF-α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-α-induced increased permeability. Asiaticoside also prevented TNF-α-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization.

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Section: Discussionsupporting

confidence: 93%

Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells

Fong

Zakaria

et al. 2015

Phytother. Res.

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“…Mechanistically, IL-9 regulated the IFN-g-and IL-17A-mediated physical properties (stress fibers formation, contractility, and stiffness) of human keratinocytes. Similar to our study, previous studies have shown the effect of IFN-g on actin cytoskeleton reorganization in various cell types (41). Similar to human keratinocytes, IL-9 suppressed the IFNgand IL-17A-induced migration of epidermoid carcinoma cells (A-431).…”

Section: Discussionsupporting

confidence: 91%

Differential Influence of IL-9 and IL-17 on Actin Cytoskeleton Regulates the Migration Potential of Human Keratinocytes

Das

Srinivasan

Srivastava

et al. 2019

The Journal of Immunology

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T cells mediate skin immune surveillance by secreting specific cytokines and regulate numerous functions of keratinocytes, including migration during homeostasis and disease pathogenesis. Keratinocyte migration is mediated mainly by proteolytic cleavage of the extracellular matrix and/or by cytoskeleton reorganization. However, the cross-talk between T cell cytokines and actomyosin machinery of human primary keratinocytes (HPKs), which is required for cytoskeleton reorganization and subsequent migration, remains poorly examined. In this study, we describe that IL-9 profoundly reduced the actin stress fibers, inhibited contractility, and reduced the cortical stiffness of HPKs, which resulted in inhibition of the migration potential of HPKs in an adhesion-and MMP-independent manner. Similarly, IL-9 inhibited the IFN-g-induced migration of HPKs by inhibiting the actomyosin machinery (actin stress fibers, contractility, and stiffness). IL-17A increased the actin stress fibers, promoted cellular contractility, and increased proteolytic collagen degradation, resulting in increased migration potential of HPKs. However, IL-9 inhibited the IL-17A-mediated HPKs migration. Mechanistically, IL-9 inhibited the IFN-g-and IL-17A-induced phosphorylation of myosin L chain in HPKs, which is a major regulator of the actomyosin cytoskeleton. Finally, in addition to HPKs, IL-9 inhibited the migration of A-431 cells (epidermoid carcinoma cells) induced either by IFN-g or IL-17A. In conclusion, our data demonstrate the influence of T cell cytokines in differentially regulating the actomyosin cytoskeleton and migration potential of human keratinocytes, which may have critical roles in skin homeostasis and pathogenesis of inflammatory diseases as well as skin malignancies.

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“…IFN-γ can also act on T cells, orchestrating CD4 + T cell and CD8 + T cell activation and differentiation, as well as apoptosis ( 18 – 24 ). Moreover, IFN-γ can directly modify the function and status of brain-resident and -specialized cell populations, including neurons, brain endothelial cells, microglial cells, and astrocytes, in a variety of inflammatory settings, including malaria ( 25 – 30 ). Combined, these observations indicate that IFN-γ may mediate ECM development by targeting a specific cell type, in a particular location, at a precise time of infection.…”

Section: Introductionmentioning

confidence: 99%

Gamma Interferon Mediates Experimental Cerebral Malaria by Signaling within Both the Hematopoietic and Nonhematopoietic Compartments

et al. 2017

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Experimental cerebral malaria (ECM) is a gamma interferon (IFN-γ)-dependent syndrome. However, whether IFN-γ promotes ECM through direct and synergistic targeting of multiple cell populations or by acting primarily on a specific responsive cell type is currently unknown. Here, using a panel of cell- and compartment-specific IFN-γ receptor 2 (IFN-γR2)-deficient mice, we show that IFN-γ causes ECM by signaling within both the hematopoietic and nonhematopoietic compartments. Mechanistically, hematopoietic and nonhematopoietic compartment-specific IFN-γR signaling exerts additive effects in orchestrating intracerebral inflammation, leading to the development of ECM. Surprisingly, mice with specific deletion of IFN-γR2 expression on myeloid cells, T cells, or neurons were completely susceptible to terminal ECM. Utilizing a reductionist in vitro system, we show that synergistic IFN-γ and tumor necrosis factor (TNF) stimulation promotes strong activation of brain blood vessel endothelial cells. Combined, our data show that within the hematopoietic compartment, IFN-γ causes ECM by acting redundantly or by targeting non-T cell or non-myeloid cell populations. Within the nonhematopoietic compartment, brain endothelial cells, but not neurons, may be the major target of IFN-γ leading to ECM development. Collectively, our data provide information on how IFN-γ mediates the development of cerebral pathology during malaria infection.

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Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration

Cited by 42 publications

References 45 publications

Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells

Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells

Differential Influence of IL-9 and IL-17 on Actin Cytoskeleton Regulates the Migration Potential of Human Keratinocytes

Gamma Interferon Mediates Experimental Cerebral Malaria by Signaling within Both the Hematopoietic and Nonhematopoietic Compartments

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