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Arvelexin from Brassica rapa suppresses NF-?B-regulated pro-inflammatory gene expression by inhibiting activation of I?B kinase.

ABSTRACT: BACKGROUND AND PURPOSE: Brassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolated from B. rapa, on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and on a model of septic shock induced by LPS. EXPERIMENTAL APPROACH: The expression of Inducible nitric oxide synthase (iNOS) and COX-2, TNF-?, IL-6 and IL-1? were determined by Western blot and/or RT-PCR respectively. To elucidate the underlying mechanism(s), activation of NF-?B activation and its pathways were investigated by electrophoretic mobility shift assay, reporter gene and Western blot assays. In addition, the in vivo anti-inflammatory effects of arvelexin were evaluated in endotoxaemia induced with LPS. KEY RESULTS: Promoter assays for iNOS and COX-2 revealed that arvelexin inhibited LPS-induced NO and prostaglandin E(2) production through the suppression of iNOS and COX-2 at the level of gene transcription. In addition, arvelexin inhibited NF-?B-dependent inflammatory responses by modulating a series of intracellular events of I?B kinase (IKK)-inhibitor ?B? (I?B?)-NF-?B signalling. Moreover, arvelexin inhibited IKK?-elicited NF-?B activation as well as iNOS and COX-2 expression. Serum levels of NO and inflammatory cytokines and mortality in mice challenged injected with LPS were significantly reduced by arvelexin. CONCLUSION AND IMPLICATIONS: Arvelexin down-regulated inflammatory iNOS, COX-2, TNF-?, IL-6 and IL-1? gene expression in macrophages interfering with the activation of IKK? and p38 mitogen-activated protein kinase, and thus, preventing NF-?B activation.

SUBMITTER: Shin JS

PROVIDER: S-EPMC3171867 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

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Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.

Shin Ji-Sun JS Noh Young-Su YS Lee Yong Sup YS Cho Young-Wuk YW Baek Nam-In NI Choi Myung-Sook MS Jeong Tae-Sook TS Kang Eunkyung E Chung Hae-Gon HG Lee Kyung-Tae KT

British journal of pharmacology 20110901 1

<h4>Background and purpose</h4>Brassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolated from B. rapa, on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and on a model of septic shock induced by LPS.<h4>Experimental approach</h4>The expression of Inducible nitric oxide synthase (iNOS) and COX-2, TNF-α, IL-6 and IL-1β were determined by Western blot ...[more]

PMID: 21434881

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Project description:Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 h after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of MCP-1 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signaling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-κB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses.

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Arvelexin from Brassica rapa suppresses NF-?B-regulated pro-inflammatory gene expression by inhibiting activation of I?B kinase.

Publications

Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.

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