Urokinase plasminogen activator mRNA is induced by IL‐1α and TNF‐α in <i>in vitro</i> acantholysis

Feliciani, Claudio; Toto, Paola; Wang, Binghe; Sauder, Daniel N.; Amerio, Paolo; Tulli, A

doi:10.1034/j.1600-0625.2002.120415.x

Cited by 50 publications

(51 citation statements)

References 29 publications

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“…Similar results were achieved by Feliciani et al 15 They demonstrated that keratinocytes synthesiz IL-1α and TNF-α. These cytokines can play a role in PV acantholysis.…”

Section: Discussionsupporting

confidence: 78%

Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

Khozeimeh¹,

Savabi²,

Esnaashari³

2014

The Journal of Contemporary Dental Practice

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Pemphigus is an autoimmune blistering disease characterized by a loss of cell adhesion result in acantholysis. Genetic factors and immunologic factors such as cytokines particularly IL-1α, IL-10, TNF-α, and TGF-β may counterpart to developing of Pemphigus. The aim of this study was to evaluate. The concentration of IL-1α, IL-10, TNF-α, TGF-β in serum of pemphigus vulgaris (PV) patients and normal individuals. Material and methods:In this analytic and descriptive study 25 patients with pemphigus vulgaris (in active phase) and 25 healthy persons were examined. Serum samples of two groups were obtained and the level of IL-1α, IL-10, TNF-α and TGF-β were measured by ELISA technique. The data were analyzed statistically by independent T test (α = 0/05).

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“…Similar results were achieved by Feliciani et al 15 They demonstrated that keratinocytes synthesiz IL-1α and TNF-α. These cytokines can play a role in PV acantholysis.…”

Section: Discussionsupporting

confidence: 78%

Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

Khozeimeh¹,

Savabi²,

Esnaashari³

2014

The Journal of Contemporary Dental Practice

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“…71 TNF-␣ has been shown to activate calpains because of a rise in the concentration of intracellular free Ca 2ϩ . 72 It is well established that TNF-␣ is elevated in the serum of PV patients, [73][74][75][76] deposited in the lesional skin, 77,78 present in the blister fluid, 74 and up-regulated in keratinocytes due to PV antibody binding 78,79 and that anti-TNF-␣ therapy with etanercept (a fusion protein of TNF-␣ receptor) can ameliorate recalcitrant PV. 80,81 During cell injury, calpain functions as a signal to mediate the influx of extracellular Ca 2ϩ after ATP depletion and endoplasmic reticulum Ca 2ϩ release.…”

Section: Discussionmentioning

confidence: 99%

Novel Mechanisms of Target Cell Death and Survival and of Therapeutic Action of IVIg in Pemphigus

Arredondo

Chernyavsky

Karaouni

et al. 2005

The American Journal of Pathology

112

139

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“…Using an organ culture model of PV, it has been demonstrated that PVIgG works together with FasL and tumor necrosis factor ␣ to induce apoptolysis (22). These and some other mediators of inflammation were found to be elevated in skin and/or serum of PV patients (16,19,(23)(24)(25).…”

Section: Pemphigus Vulgaris (Pv)mentioning

confidence: 99%

Antimitochondrial Autoantibodies in Pemphigus Vulgaris

Marchenko

Chernyavsky

Arredondo

et al. 2010

Journal of Biological Chemistry

115

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A loss of epidermal cohesion in pemphigus vulgaris (PV) results from autoantibody action on keratinocytes (KCs) activating the signaling kinases and executioner caspases that damage KCs, causing their shrinkage, detachment from neighboring cells, and rounding up (apoptolysis). In this study, we found that PV antibody binding leads to activation of epidermal growth factor receptor kinase, Src, p38 MAPK, and JNK in KCs with time pattern variations from patient to patient. Both extrinsic and intrinsic apoptotic pathways were also activated. Although Fas ligand neutralizing antibody could inhibit the former pathway, the mechanism of activation of the latter remained unknown. PV antibodies increased cytochrome c release, suggesting damage to mitochondria. The immunoblotting experiments revealed penetration of PVIgG into the subcellular mitochondrial fraction. The antimitochondrial antibodies from different PV patients recognized distinct combinations of antigens with apparent molecular sizes of 25, 30, 35, 57, 60, and 100 kDa. Antimitochondrial antibodies were pathogenic because their absorption abolished the ability of PVIgG to cause keratinocyte detachment both in vitro and in vivo. The downstream signaling of antimitochondrial antibodies involved JNK and late p38 MAPK activation, whereas the signaling of anti-desmoglein 3 (Dsg3) antibody involved JNK and biphasic p38 MAPK activation. Using KCs grown from Dsg3؊/؊ mice, we determined that Dsg3 did not serve as a surrogate antigen allowing antimitochondrial antibodies to enter KCs. The PVIgG-induced activation of epidermal growth factor receptor and Src was affected neither in Dsg3KCs nor due to absorption of antimitochondrial antibodies. These results demonstrated that apoptolysis in PV is a complex process initiated by at least three classes of autoantibodies directed against desmosomal, mitochondrial, and other keratinocyte self-antigens. These autoantibodies synergize with the proapoptotic serum and tissue factors to trigger both extrinsic and intrinsic pathways of cell death and break the epidermal cohesion, leading to blisters. Further elucidation of the primary signaling events downstream of PV autoantigens will be crucial for the development of a more successful therapy for PV patients.Pemphigus vulgaris (PV) 3 is an IgG autoantibody-mediated disease of skin and mucosa caused by a loss of epidermal cohesion and manifested by progressive blistering and non-healing erosions. The mechanism of detachment of keratinocytes (KCs) in PV, termed acantholysis, is a subject of intensive research. Elucidation of the pathophysiologic mechanism of acantholysis should facilitate development of novel pharmacologic approaches to prevent and treat blistering without systemic corticosteroids, a mainstay of treatment of PV patients. Acantholysis can be blocked both by inhibitors of signaling kinases, such as p38 MAPK (3), mammalian target of rapamycin (4), Src, and epidermal growth factor receptor (EGFR) kinase (2, 4 -7) and by other tyrosine kinases, phospholipase C, calmodulin...

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Urokinase plasminogen activator mRNA is induced by IL‐1α and TNF‐α in in vitro acantholysis

Cited by 50 publications

References 29 publications

Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

Evaluation of Interleukin-1α, Interleukin-10, Tumor Necrosis Factor-α and transforming Growth Factor-β in the Serum of Patients with Pemphigus Vulgaris

Novel Mechanisms of Target Cell Death and Survival and of Therapeutic Action of IVIg in Pemphigus

Antimitochondrial Autoantibodies in Pemphigus Vulgaris

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