Tumor necrosis factor-alpha and the cytokine network in psoriasis

Brotas, Arles Martins; Cunha, José Marcos Telles da; Lago, Eduardo Henrique Jorge; Machado, Cristiane Chaves Nascentes; Carneiro, Sueli Coelho da Silva

doi:10.1590/s0365-05962012000500001

Cited by 42 publications

(44 citation statements)

References 55 publications

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“…Serwin et al [40] found that serum TNFR-1 levels were significantly increased in patients with psoriasis compared with those in controls. Brotas et al [41] reported that TNF- α has various effects on the cellular level in psoriasis. Coimbra et al [42] found no differences in TNF levels between patients and controls.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Lipocalin 2, Clusterin, Soluble Tumor Necrosis Factor Receptor-1, Interleukin-6, Homocysteine, and Uric Acid Levels in Patients with Psoriasis

Ataseven¹,

Keşli

Kurtipek³

et al. 2014

Disease Markers

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Background. Chronic inflammation may play a role in psoriasis pathogenesis. Lipocalin 2, clusterin, soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6, homocysteine, and uric acid are inflammatory and/or biochemical markers. However, both the roles of these markers and the pathogenesis of psoriasis are unknown. Objective. The aim of this study was to investigate serum levels of lipocalin 2, clusterin, sTNFR-1, interleukin-6, homocysteine, and uric acid in patients and controls groups. Methods. Fifty-six patients with psoriasis and 33 healthy controls were included in the study. Serum concentrations of the markers were evaluated by ELISA. The Psoriasis Area and Severity Index (PASI) was evaluated in all psoriasis patients. Body mass index (BMI) was calculated by dividing weight (kg) by height (m) squared. Results. The serum value of lipocalin and sTNFR-1 were significantly higher in psoriasis patients than in controls (resp., P < 0.001, P < 0.05). The others showed no significant differences between psoriasis and the control groups (all of them P > 0.05). The mean PASI score in the patient group was 8.3 ± 6.5. Conclusions. These findings suggest that lipocalin 2 and sTNFR-1 might play a role in the pathogenesis of psoriasis and can be used as markers of the disease.

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Section: Discussionmentioning

confidence: 99%

Assessment of Lipocalin 2, Clusterin, Soluble Tumor Necrosis Factor Receptor-1, Interleukin-6, Homocysteine, and Uric Acid Levels in Patients with Psoriasis

Ataseven¹,

Keşli

Kurtipek³

et al. 2014

Disease Markers

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“…Furthermore, with the extensive cross-talk between keratinocytes and immune cells in psoriasis, it is unclear which is the major source of these cytokines, and the role of activated keratinocytes in cytokine production cannot be excluded. In fact, keratinocytes are thought to be the primary producers of IL-1 in the skin (Brotas et al, 2012). To stimulate cytokine production by keratinocytes, we used TPA, which is a known inducer of the keratinocyte inflammatory response (Kim et al, 2014).…”

Section: Mmf-induced Effects In Keratinocytesmentioning

confidence: 99%

The Antipsoriatic Agent Monomethylfumarate Has Antiproliferative, Prodifferentiative, and Anti-Inflammatory Effects on Keratinocytes

Helwa

Patel

Karempelis

et al. 2014

J Pharmacol Exp Ther

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Monomethylfumarate (MMF) is thought to be the bioactive ingredient of the drug Fumaderm (Biogen Idec, Cambridge, MA), licensed in Germany since 1994 for the treatment of moderate-tosevere psoriasis. Psoriasis is a common inflammatory hyperproliferative skin disorder that involves cross-talk between different cell types, including immune cells and keratinocytes. Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation, and inflammation, with the psoriatic cytokine network maintained by communication between immune cells and keratinocytes. Recently, there is increasing evidence regarding the pivotal role of keratinocytes in mediating the disease process, and these cells can be regarded as safe therapeutic targets. From the data available on human subjects treated with Fumaderm, MMF is an effective antipsoriatic agent with known effects on immune cells. However, little is known about its direct effects on keratinocytes. We hypothesized that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes. Indeed, MMF dose-dependently inhibited [ 3 H]thymidine incorporation into DNA, indicating a direct antiproliferative action on keratinocytes. MMF significantly increased the protein level of keratin 10, the early keratinocyte differentiation marker, and the activity of transglutaminase, a late differentiation marker. These results are consistent with an ability of MMF to promote keratinocyte differentiation and inhibit proliferation, thereby improving psoriatic lesions. In 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced keratinocytes, MMF significantly inhibited the expression of the proinflammatory cytokines, tumor necrosis factor-a (TNFa), interleukin-6, and interleukin-1a as well as the production of TNFa. Our results support the notion that MMF has direct antiproliferative, prodifferentiative, and anti-inflammatory effects on keratinocytes, highlighting its potential use as a multifactorial antipsoriatic agent.

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“…TNF-α is secreted by a variety of cells such as macrophages, monocytes, neutrophils, T cells, natural killer cells, adipocytes, and fibroblasts (Fahey et al, 1995; Jovinge et al, 1996; Cawthorn and Sethi, 2008; Ambler et al, 2012; Brotas et al, 2012; Zakka et al, 2012), and its signaling is transduced through TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Soluble TNF-α binds preferentially to TNFR1, which is expressed in neurons (Brambilla et al, 2011) whereas transmembrane TNF-α binds to TNFR2, which is mainly expressed in immune cells such as those of the myeloid lineage, lymphocytes, and macrophages (McCoy and Tansey, 2008).…”

Section: Tumor Necrosis Factor-αmentioning

confidence: 99%

Growth factors in synaptic function

Poon

Choi

Park

2013

Front. Synaptic Neurosci.

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Synapses are increasingly recognized as key structures that malfunction in disorders like schizophrenia, mental retardation, and neurodegenerative diseases. The importance and complexity of the synapse has fuelled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. In this regard, neurotrophic factors such as netrin, Wnt, transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and others have gained prominence for their ability to regulate synaptic function. Several of these factors were first implicated in neuroprotection, neuronal growth, and axon guidance. However, their roles in synaptic development and function have become increasingly clear, and the downstream signaling pathways employed by these factors have begun to be elucidated. In this review, we will address the role of these factors and their downstream effectors in synaptic function in vivo and in cultured neurons.

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Tumor necrosis factor-alpha and the cytokine network in psoriasis

Cited by 42 publications

References 55 publications

Assessment of Lipocalin 2, Clusterin, Soluble Tumor Necrosis Factor Receptor-1, Interleukin-6, Homocysteine, and Uric Acid Levels in Patients with Psoriasis

Assessment of Lipocalin 2, Clusterin, Soluble Tumor Necrosis Factor Receptor-1, Interleukin-6, Homocysteine, and Uric Acid Levels in Patients with Psoriasis

The Antipsoriatic Agent Monomethylfumarate Has Antiproliferative, Prodifferentiative, and Anti-Inflammatory Effects on Keratinocytes

Growth factors in synaptic function

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