4-Hydroxynonenal prevents NF-κB activation and TNF expression by inhibiting IκB phosphorylation and subsequent proteolysis

Page, Sharon; Kreusel, Ursula; Haas, Monika; Baumgartner, Bastian; Loidl, Günther; Hayn, Manuel; Neumeier, D.; Brand, Korbinian

doi:10.1016/s0021-9150(99)80032-x

Cited by 4 publications

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“…1 and 2), the two classical anti-inflammatory agents, aspirin and salicylic acid, have been shown to act in vitro through inhibition of IkB degradation and the subsequent inhibition of NF-kB activation (25), (26). Other anti-inflammatory agents reported for inhibition (at mM concentration range) of NF-kB activation and the subsequent TNF release include resveratrol (1) and quercetin (19), (21), (27), nordihydroguaiaretic acid (2), butylated hydroxyanisol and tetrahydropapaveralione (6) (11), curcumin (3) (12), (28), myricetin (27), epigallocatechingallate (29), 4-hydroxy-2-nonenal (30), and capsaicin (7) (31). In experiments using BALB/c mice, however, dietary capsaicin (7) did not show the expected immunosuppression and a rather high level of TNF was detected following capsaicin (7) feeding suggesting possible enhancement of the immune functions (32).…”

Section: Inhibition Of Tnf Production and Secretionmentioning

confidence: 99%

Natural Inhibitors of Tumour Necrosis Factor-α Production, Secretion and Function

Habtemariam

2000

Planta Med

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Tumour necrosis factor-a a (TNF), originally discovered by its antitumor activity, is one of the most pleotropic cytokines acting as a host defence factor in immunologic and inflammatory responses. Although the antitumour activity and mediation of inflammation by TNF could be beneficial to the host, unregulated TNF is now known to be the basis for development of various diseases including septic shock, the wasting disease, cachexia, and various inflammatory and/or autoimmune diseases. With an attempt to find potential therapeutic agents for TNF-mediated diseases, research during the last decade has led in the identification of well over one hundred natural inhibitors of either TNF production/secretion or function. This review summarises the structures, mechanism of action and therapeutic potential of these natural products.Key words: TNF, natural inhibitors, adhesion molecules, NF-k kB, cAMP, inflammation, cytotoxicity. IntroductionTumour necrosis factor-a (TNF; also known as cachectin) was originally discovered by its antitumour activity, but it is now recognised to be one of the most pleotropic cytokines acting as a host defence factor in immunologic and inflammatory responses (1), (2). Among its many different activities, TNF has effects on the vascular endothelium which leads to upregulation of various cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leucocyte adhesion molecule-1 (ELAM-1) (3). The regulated expression of these adhesion molecules and their counter-receptors on leucocytes mediates the adhesion and extravasation of white blood cells during inflammatory reaction. While mediation of inflammation and anti-tumour activity by TNF could be beneficial to the host, overproduction of TNF is the basis for the development of various diseases. There is now overwhelming evidence to suggest that TNF mediates the wasting disease, cachexia, associated with chronic diseases such as cancer and AIDS (4), (5). TNF also plays pivotal roles in the development of pathologies such as disseminated intravascular coagulation and death in septic shock and cerebral malaria (6), (7) and a range of inflammatory diseases including asthma (8) and dermatitis, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, rheumatoid arthritis, multiple sclerosis and immunological diseases (9). It is thus clear that suppression of TNF production/release or inhibition of its function could benefit in the treatment of these TNF-mediated diseases. Potential Targets for Natural ProductsThe various target sites for modulation of TNF production and function by antibodies and pharmacological agents have been reviewed recently (9), (10). Potential target sites for inhibitory small molecular weight natural products could be broadly divided into three areas: i) inhibition of TNF production and secretion, ii) TNF receptor antagonism, and iii) inhibition of TNF function through modulation of its signal transduction pathway(s). During the 1990©s,...

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Section: Inhibition Of Tnf Production and Secretionmentioning

confidence: 99%

Natural Inhibitors of Tumour Necrosis Factor-α Production, Secretion and Function

Habtemariam

2000

Planta Med

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“…4 NF-B activity is modulated by various stimuli related to oncogenesis, including many cytokines, viral products, oncoproteins as well as physical, oxidative and genotoxic stress. 4,9,11,12 This activation involves the phosphorylation of IB, which is subsequently degraded in an ubiquitin-dependent step by the proteasome, thereby allowing the liberated NF-B dimer to translocate to the nuclear compartment. 1,2 Within the nucleus, NF-B is involved in the coordinated expression of numerous target genes, for example, cytokines and chemokines, growth factors, antiapoptotic genes, cell adhesion molecules, proteolytic enzymes, angiogenic factors as well as procoagulatory molecules.…”

Section: Introductionmentioning

confidence: 99%

Increased IκB kinase activity is associated with activated NF-κB in acute myeloid blasts

et al. 2002

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“…B. stδrker oxidiertes LDL [13]. Wδhrend der Oxidation von LDL beobachtet man eine Zunahme von 4-Hydroxynonenal (HNE) oder Lysophosphatidylcholin, fόr die ebenfalls deutliche Hemmeffekte auf das NF-KB-System nachgewiesen wurden [19,20]. So wurde gezeigt, daί eine Prδinkubation mit HNE eine selektive.…”

Section: Rolle Von Nf-bei Entzόndung Und Malignitδtunclassified

“…So wurde gezeigt, daί eine Prδinkubation mit HNE eine selektive. Hemmung der -Phosphorylierung und -Proteolyse bewirkt und damit die NF--Trans l okation, die -sowie TNF-oder IL-8-Promotor-abhδngige Transkription und die Expression von NF-KB-Zielgenen negativ beeinfluίt [19]. Eine Dysregulation im Sinne einer Inhibierung von NF-kφnnte unter bestimmten Bedingungen protektive, entzόndliche Reparatur-oder Immunmechanismen stφren und damit zur Chronifizierung des Geschehens und zur Bildung von Schaumzellen beitragen.…”

Section: Rolle Von Nf-bei Entzόndung Und Malignitδtunclassified

Hoppe-Seyler-Preis

2001

LaboratoriumsMedizin

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4-Hydroxynonenal prevents NF-κB activation and TNF expression by inhibiting IκB phosphorylation and subsequent proteolysis

Cited by 4 publications

References 0 publications

Natural Inhibitors of Tumour Necrosis Factor-α Production, Secretion and Function

Natural Inhibitors of Tumour Necrosis Factor-α Production, Secretion and Function

Increased IκB kinase activity is associated with activated NF-κB in acute myeloid blasts

Hoppe-Seyler-Preis

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