Natural products as targeted modulators of the nuclear factor-<i>κ</i>B pathway

Bremner, Paul; Heinrich, Michael

doi:10.1211/0022357021778637

Cited by 289 publications

(182 citation statements)

References 166 publications

(167 reference statements)

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“…NF-B, which forms a homo-or heterodimer complex, regulates inflammatory genes such as COX-2, iNOS, TNF-␣, and IL-1␤ (40), and many phytochemicals that inhibit NF-B can reduce RA in animal and human studies (41,42). In this study, stable Pin1 overexpression caused both the sustained nuclear translocation of p65 and increased NF-B transcription.…”

Section: Discussionmentioning

confidence: 62%

Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis

Jeong

Pokharel

Lim

et al. 2009

The Journal of Immunology

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints and subsequent destruction of cartilage and bone. Inflammatory mediators such as PGs and proinflammatory cytokines contribute to RA progress. Pin1, a peptidyl prolyl isomerase, plays important pathophysiological roles in several diseases, including cancer and neurodegeneration. We found that both Pin1 and cyclooxygenase-2 (COX-2) were highly expressed in ankle tissues of type II collagen-induced RA mice. HTB-94 cells overexpressing Pin1 and primary cultured human chondrocytes showed increased basal expression of proinflammatory proteins (COX-2, inducible NO synthase, TNF-α, and IL-1β). Site-directed mutagenesis revealed that Pin1-mediated transcriptional activation of COX-2 was coordinately regulated by NF-κB, CREB, and C/EBP. Gel shift, reporter gene, and Western blot analyses confirmed that NF-κB, CREB, and C/EBP were consistently activated in chondrocytes overexpressing Pin1. Treatment of RA mice with juglone, a chemical inhibitor of Pin1, significantly reduced RA progress and COX-2 expression in the ankle tissues. Moreover, juglone dose dependently decreased the basal COX-2 expression in primary cultured chondrocytes from RA patients. These results demonstrate that Pin1 induction during RA progress stimulates proinflammatory protein expression by activating NF-κB, CREB, and C/EBP, and suggest that Pin1 is a potential therapeutic target of RA.

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Section: Discussionmentioning

confidence: 62%

Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis

Jeong

Pokharel

Lim

et al. 2009

The Journal of Immunology

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“…(2) isolated from the echinoderm Comanthus parvicirrus and the isomalabaricanes stellettin A (3) and stellettin B (4) isolated from the sponge Rhabdastrella globostellata possess lactone rings with -unsaturated carbonyl groups which may be responsible for the latter's interferences with IKK and with the binding of NF-B to DNA as described previously for other NF-B-inhibiting natural products [21]. 6-methoxy-comaparvin-5-methyl ether (1) was the only compound shown to strongly inhibit the proteolytic activity of the 26S proteasome at the test concentration of 100 g/mL.…”

Section: Discussionmentioning

confidence: 98%

“…The two NF-B-inhibiting marine natural products macrolide bryostatin 1 isolated from a bryozoan [56] and salinosporamide A isolated from a bacterium [24] are currently in clinical trials [58]. Several ecological reasons why marine natural products may inhibit NF-B have been established [20,21,[59][60][61][62][63][64][65][66][67][68][69].…”

Section: Discussionmentioning

confidence: 99%

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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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“…As a result of these phenomena, NF-kB translocates into the nucleus and activates the transcription of target genes. 9 The efficacy of the combination of inhaled corticosteroids (ICSs) with long-acting b 2 -agonists (LABAs) in the therapy of asthma has been widely demonstrated. 10 A possible explanation for this efficacy is represented by a synergistic interaction between ICSs and LABAs at a molecular level.…”

mentioning

confidence: 99%

Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

Pace¹,

Gagliardo²,

Melis³

et al. 2004

Journal of Allergy and Clinical Immunology

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Background: In asthma T cells are characterized by an increased activation state and by reduced apoptosis. Objective: Because the clinical efficacy of inhaled corticosteroids combined with long-acting b 2 -agonists has been widely demonstrated in asthma, we studied, in vitro, the effect of fluticasone propionate (FP) and salmeterol alone and in combination on the activation and apoptosis of peripheral blood T cells (PBTs), on the expression of phosphorylated nuclear factor kB inhibitor (IkBa), and on the nuclear translocation of glucocorticoid receptor (GR) in PBTs from asthmatic subjects. Methods: Apoptosis was evaluated on the basis of annexin V binding, whereas the expression of caspases 8 and 3 and phosphorylated IkBa, as well as the nuclear translocation of the GR, were evaluated by means of Western blot analysis. Results: FP alone increases and salmeterol alone does not affect T-cell apoptosis. The combination of FP and salmeterol significantly increases PBT apoptosis in comparison with FP alone. FP at the lower concentration, when combined with salmeterol, is equivalent to FP at the higher concentration in inducing PBT apoptosis. The synergy in the induction of cell apoptosis is associated with more efficient activation of caspases 8 and 3. FP plus salmeterol is also able to synergistically reduce the expression of phosphorylated IkBa, thus limiting nuclear factor kB activation. The synergy was related to an increased nuclear translocation of the GR. Conclusion: This study shows that the combination of FP and salmeterol is able to control PBT activation in asthmatic patients more efficiently than FP alone and with a lower concentration of

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Natural products as targeted modulators of the nuclear factor-κB pathway

Cited by 289 publications

References 166 publications

Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis

Novel Role of Pin1 Induction in Type II Collagen-Mediated Rheumatoid Arthritis

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

Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

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