Transcription Factor RelA

Publication Title: 
Genes & Development

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-?B activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice).

Author(s): 
Osorio, Fernando G.
B·rcena, Clea
Soria-Valles, Clara
Ramsay, Andrew J.
de Carlos, FÈlix
Cobo, Juan
Fueyo, Antonio
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Publication Title: 
International Immunopharmacology

The aim of this study was to investigate the mechanisms of action of Dihydroarteannuin (DHA), a semi-synthesized agent from the starting material artemisinin extracted from the Chinese Traditional Herbs Artemisia annua, on ameliorating the symptoms of lupus on BXSB mice. The concentration of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice was determined by the ELISA method. NF-kappaB protein expression and translocation were assayed by the EMSA method and laser confocal scanning microscopy method, respectively.

Author(s): 
Li, Wei-dong
Dong, Yan-jun
Tu, You-you
Lin, Zhi-bin
Publication Title: 
Molecular Cancer Therapeutics

Pinitol (3-O-methyl-chiroinositol), a component of traditional Ayurvedic medicine (talisapatra), has been shown to exhibit anti-inflammatory and antidiabetic activities through undefined mechanisms. Because the transcription factor nuclear factor-kappaB (NF-kappaB) has been linked with inflammatory diseases, including insulin resistance, we hypothesized that pinitol must mediate its effects through modulation of NF-kappaB activation pathway. We found that pinitol suppressed NF-kappaB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type.

Author(s): 
Sethi, Gautam
Ahn, Kwang Seok
Sung, Bokyung
Aggarwal, Bharat B.
Publication Title: 
Molecular Cancer Therapeutics

Pinitol (3-O-methyl-chiroinositol), a component of traditional Ayurvedic medicine (talisapatra), has been shown to exhibit anti-inflammatory and antidiabetic activities through undefined mechanisms. Because the transcription factor nuclear factor-kappaB (NF-kappaB) has been linked with inflammatory diseases, including insulin resistance, we hypothesized that pinitol must mediate its effects through modulation of NF-kappaB activation pathway. We found that pinitol suppressed NF-kappaB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type.

Author(s): 
Sethi, Gautam
Ahn, Kwang Seok
Sung, Bokyung
Aggarwal, Bharat B.
Publication Title: 
Journal of Ethnopharmacology

AIM OF THIS STUDY: Cardiospermum halicacabum L. is well known for its anti-inflammatory, analgesic and antipyretic activities. It has been used in Ayurveda and folk medicine for the treatment of rheumatism, fever and earache. But its mechanism of anti-inflammatory and analgesic action is still unclear, hence in this context, the objective of our study is to reveal the mechanism of anti-inflammatory and analgesic activity of Cardiospermum halicacabum L. which would form an additional proof to the traditional knowledge of Cardiospermum halicacabum L.

Author(s): 
Sheeba, M. S.
Asha, V. V.
Publication Title: 
The Journal of Biological Chemistry

Activation of NFkappaB is a fundamental cellular event central to all inflammatory diseases. Hepatocyte growth factor (HGF) ameliorates both acute and chronic inflammation in a multitude of organ systems through modulating NFkappaB activity; nevertheless, the exact molecular mechanism remains uncertain. Here we report that HGF through inactivation of GSK3beta suppresses NFkappaB p65 phosphorylation specifically at position Ser-468.

Author(s): 
Gong, Rujun
Rifai, Abdalla
Ge, Yan
Chen, Shan
Dworkin, Lance D.
Publication Title: 
Free Radical Biology & Medicine

Apigenin, a plant flavone, potentially activates wild-type p53 and induces apoptosis in cancer cells. We conducted detailed studies to understand its mechanism of action. Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner.

Author(s): 
Shukla, Sanjeev
Gupta, Sanjay
Publication Title: 
The Biochemical Journal

GA (gambogic acid) is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi with a long history of use as a complementary and alternative medicine. The antitumour activity of GA has been well demonstrated and is thought to arise partly from the associated anti-inflammatory activity. Recent studies have indicated that the antitumour activity of GA is mediated by its ligation of TfR1 (transferrin receptor-1).

Author(s): 
Palempalli, Umamaheshwari D.
Gandhi, Ujjawal
Kalantari, Parisa
Vunta, Hema
Arner, Ryan J.
Narayan, Vivek
Ravindran, Anand
Prabhu, K. Sandeep
Publication Title: 
Thrombosis and Haemostasis

High-mobility group box 1 protein (HMGB1), an abundant nuclear protein, was recently established as a proinflammatory mediator of experimental sepsis. Although extracellular HMGB1 has been found in atherosclerotic plaques, its potential role in the pathogenesis of atherothrombosis remains elusive. In the present study, we determined whether HMGB1 induces tissue factor (TF) expression in vascular endothelial cells (ECs) and macrophages. Our data showed that HMGB1 stimulated ECs to express TF (but not TF pathway inhibitor) mRNA and protein in a concentration- and time-dependent manner.

Author(s): 
Lv, Ben
Wang, Haichao
Tang, Yiting
Fan, Zhang
Xiao, Xianzhong
Chen, Fangping
Publication Title: 
Apoptosis: An International Journal on Programmed Cell Death

The tumor necrosis factor (TNF) receptor super family comprises of members that induce two distinct signaling cascades, leading to either cell survival or apoptosis. However, in prostate cancer (PCa), TNF-mediated prosurvival signaling is the predominant pathway that leads to cell survival and resistance to therapy. Although inhibition of TNF signaling by pharmacological agents or monoclonal antibodies has gained importance in the field of cancer therapy, toxicity to normal cells has impaired their extensive use for cancer treatment.

Author(s): 
Srinivasan, Sowmyalakshmi
Kumar, Raj
Koduru, Srinivas
Chandramouli, Aaditya
Damodaran, Chendil

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