NF-κB inhibition by ω-3 fatty acids modulates  LPS-stimulated macrophage TNF-α transcription

Novak, Todd E.; Babcock, Tricia A.; Jho, David H.; Helton, W. Scott; Espat, N. Joseph

doi:10.1152/ajplung.00077.2002

Cited by 363 publications

(281 citation statements)

References 23 publications

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“…Our results are in accord with Poerschmann et al, who showed that the unsaturation index of FAs in algae and bacteria tends to be higher in colder climates than in warmer climates [70,74]. -3 PUFAs, but not -6 PUFAs, mono-unsaturated FAs or saturated FAs, have been shown to be potent NF-B inhibitors [75][76][77][78][79][80]. One would hence have expected the CCMP 1619 extract, which has a twelve times higher concentration in -3 PUFA than the remaining extracts, to stand out as the strongest NF-B inhibitor.…”

Section: Discussionsupporting

confidence: 93%

The inhibition of TNF-α-induced NF-κB activation by marine natural products

Folmer

Jaspars

Solano

et al. 2009

Biochemical Pharmacology

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, et al.. The inhibition of TNF-α induced NF-κB activation by marine natural products. Biochemical Pharmacology, Elsevier, 2009, 78 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 AbstractThe deregulated activation of NF-B is associated with cancer development and inflammatory diseases. With the aim to find new NF-B inhibitors, we purified and characterized compounds from extracts of the Fijian sponge Rhabdastrella globostellata, the crinoid Comanthus parvicirrus, the soft corals Sarcophyton sp. nov. and Sinularia sp., and the gorgonian Subergorgia sp. after an initial screening of 266 extracts from different marine origins.Results obtained show that selected purified compounds had a cytotoxic effect on the human leukaemia cell line K562, inhibited both TNF--induced NF-B-DNA binding as well as TNF- induced IB degradation and nuclear translocation of p50/p65. Furthermore, we observed inhibition of NF-B activation induced by an overexpression of TNFR1, TRAF2, TRADD, or IKK Interestingly, natural products inhibited IKK kinase as well as the 26S proteasome proteolytic activity.

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Section: Discussionsupporting

confidence: 93%

The inhibition of TNF-α-induced NF-κB activation by marine natural products

Folmer

Jaspars

Solano

et al. 2009

Biochemical Pharmacology

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“…We have shown EPA to prevent both degradation of I-kBa and nuclear accumulation of NF-kB in murine myotubes in the presence of PIF , through attenuation of upstream signalling pathways. Omega-3 polyunsaturated fatty acids have also been shown to inhibit I-kB phosphorylation and NF-kB activation in murine macrophages, although the mechanism is not known (Novak et al, 2003). This manuscript provides experimental evidence to support the claim that PIF induces proteasome expression through activation of nuclear binding of NF-kB.…”

Section: Discussionmentioning

confidence: 65%

NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin–proteasome system in skeletal muscle

2005

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Loss of skeletal muscle in cancer cachexia has a negative effect on both morbidity and mortality. The role of nuclear factor-kB (NFkB) in regulating muscle protein degradation and expression of the ubiquitin -proteasome proteolytic pathway in response to a tumour cachectic factor, proteolysis-inducing factor (PIF), has been studied by creating stable, transdominant-negative, muscle cell lines. Murine C 2 C 12 myoblasts were transfected with plasmids with a CMV promoter that had mutations at the serine phosphorylation sites required for degradation of I-kBa, an NF-kB inhibitory protein, and allowed to differentiate into myotubes. Proteolysis-inducing factor induced degradation of I-kBa, nuclear accumulation of NF-kB and an increase in luciferase reporter gene activity in myotubes containing wild-type, but not mutant, I-kBa proteins. Proteolysis-inducing factor also induced total protein degradation and loss of the myofibrillar protein myosin in myotubes containing wild-type, but not mutant, plasmids at the same concentrations as those causing activation of NF-kB. Proteolysis-inducing factor also induced increased expression of the ubiquitinproteasome pathway, as determined by 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the b-subunits of the proteasome, protein expression of 20S a-subunits and the 19S subunits MSS1 and p42, as well as the ubiquitin conjugating enzyme, E2 14k , in cells containing wild-type, but not mutant, I-kBa. The ability of mutant I-kBa to inhibit PIF-induced protein degradation, as well as expression of the ubiquitin -proteasome pathway, confirms that both of these responses depend on initiation of transcription by NF-kB.

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“…Thus EPA, which prevents nuclear migration of NF-kB in murine myotubes in response to PIF by stabilising the cytosolic I-kB/NF-kB complex (Whitehouse and Tisdale, 2003), possibly by interfering with I-kB phosphorylation (Novak et al, 2003), has been shown to attenuate the development of further weight loss in weight-losing patients with pancreatic cancer (Wigmore et al, 2000) and produce an increase in lean body mass when combined with a high protein energy dense nutritional supplement (Barber et al, 1999). The anti-inflammatory agent, ibuprofen, has been shown to inhibit constitutive activation of NFkB and IKKa in prostate cancer cells (Palayoor et al, 1999), and when combined with megestrol acetate produced an increase in body weight in gastrointestinal cancer patients (McMillan et al, 1999), while megestrol acetate alone produced a decrease in body weight.…”

Section: Discussionmentioning

confidence: 99%

Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-κB activation

2004

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The potential for inhibitors of nuclear factor-kB (NF-kB) activation to act as inhibitors of muscle protein degradation in cancer cachexia has been evaluated both in vitro and in vivo. Activation of NF-kB is important in the induction of proteasome expression and protein degradation by the tumour factor, proteolysis-inducing factor (PIF), since the cell permeable NF-kB inhibitor SN50 (18 mM) attenuated the expression of 20S proteasome a-subunits, two subunits of the 19S regulator MSS1 and p42, and the ubiquitinconjugating enzyme, E2 14k , as well as the decrease in myosin expression in murine myotubes. To assess the potential therapeutic benefit of NF-kB inhibitors on muscle atrophy in cancer cachexia, two potential inhibitors were employed; curcumin (50 mM) and resveratrol (30 mM). Both agents completely attenuated total protein degradation in murine myotubes at all concentrations of PIF, and attenuated the PIF-induced increase in expression of the ubiquitin -proteasome proteolytic pathway, as determined by the 'chymotrypsin-like' enzyme activity, proteasome subunits and E2 14k . However, curcumin (150 and 300 mg kg À1 ) was ineffective in preventing weight loss and muscle protein degradation in mice bearing the MAC16 tumour, whereas resveratrol (1 mg kg À1 ) significantly attenuated weight loss and protein degradation in skeletal muscle, and produced a significant reduction in NF-kB DNAbinding activity. The inactivity of curcumin was probably due to a low bioavailability. These results suggest that agents which inhibit nuclear translocation of NF-kB may prove useful for the treatment of muscle wasting in cancer cachexia.

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NF-κB inhibition by ω-3 fatty acids modulates LPS-stimulated macrophage TNF-α transcription

Cited by 363 publications

References 23 publications

The inhibition of TNF-α-induced NF-κB activation by marine natural products

The inhibition of TNF-α-induced NF-κB activation by marine natural products

NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin–proteasome system in skeletal muscle

Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-κB activation

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