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Find video protocols related to scientific articles indexed in Pubmed.
I?B? augments IL-12- and IL-18-mediated IFN-? production in human NK cells.
Blood
PUBLISHED: 01-11-2011
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Interferon-? (IFN-?) production by natural killer (NK) cells and cytotoxic lymphocytes is a key component of innate and adaptive immune responses. Because inhibitor of ?B-? (I?B?), a Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) inducible transcription factor, regulates IFN-? production in KG-1 cells, we tested I?B?s role in the classic lymphocyte pathway of IL-12/IL-18-induced IFN-?. Upon stimulation with IL-12/IL-18, monocyte-depleted human peripheral blood lymphocytes expressed the 79-kDa form of I?B? and released IFN-?. CD56(+) NK cells were shown to be the I?B?-producing lymphocyte subpopulation, which also released abundant IFN-? in response to IL-12/IL-18. Importantly, I?B? was undetectable in CD56(-) lymphocytes where IFN-? release was 10-fold lower. In addition, small interfering RNA knockdown of I?B? suppressed IFN-? expression in CD56(+) cells. The association of I?B? with the IFN-? promoter was documented by chromatin immunoprecipitation. IFN-? promoter activity from I?B? overexpression was confirmed by luciferase reporter assay. Finally, I?B? coprecipitated with p65 and p50 NF-?B in NK cells in response to IL-12/IL-18, suggesting that I?B?s effects on IFN-? promoter activity are coregulated by NF-?B. These results suggest that I?B? functions as an important regulator of IFN-? in human NK cells, further expanding the class of I?B?-modulated genes.
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A novel role for IkappaBzeta in the regulation of IFNgamma production.
PLoS ONE
PUBLISHED: 06-09-2009
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IkappaBzeta is a novel member of the IkappaB family of NFkappaB regulators, which modulates NFkappaB activity in the nucleus, rather than controlling its nuclear translocation. IkappaBzeta is specifically induced by IL-1beta and several TLR ligands and positively regulates NFkappaB-mediated transcription of genes such as IL-6 and NGAL as an NFkappaB binding co-factor. We recently reported that the IL-1 family cytokines, IL-1beta and IL-18, strongly synergize with TNFalpha for IFNgamma production in KG-1 cells, whereas the same cytokines alone have minimal effects on IFNgamma production. Given the striking similarities between the IL-1R and IL-18R signaling pathways we hypothesized that a common signaling event or gene product downstream of these receptors is responsible for the observed synergy. We investigated IkappaBzeta protein expression in KG-1 cells upon stimulation with IL-1beta, IL-18 and TNFalpha. Our results demonstrated that IL-18, as well as IL-1beta, induced moderate IkappaBzeta expression in KG-1 cells. However, TNFalpha synergized with IL-1beta and IL-18, whereas by itself it had a minimal effect on IkappaBzeta expression. NFkappaB inhibition resulted in decreased IL-1beta/IL-18/TNFalpha-stimulated IFNgamma release. Moreover, silencing of IkappaBzeta expression led to a specific decrease in IFNgamma production. Overall, our data suggests that IkappaBzeta positively regulates NFkappaB-mediated IFNgamma production in KG-1 cells.
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Monocyte derived microvesicles deliver a cell death message via encapsulated caspase-1.
PLoS ONE
PUBLISHED: 05-05-2009
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Apoptosis depends upon the activation of intracellular caspases which are classically induced by either an intrinsic (mitochondrial based) or extrinsic (cytokine) pathway. However, in the process of explaining how endotoxin activated monocytes are able to induce apoptosis of vascular smooth muscle cells when co-cultured, we uncovered a transcellular apoptosis inducing pathway that utilizes caspase-1 containing microvesicles. Endotoxin stimulated monocytes induce the cell death of VSMCs but this activity is found in 100,000 g pellets of cell free supernatants of these monocytes. This activity is not a direct effect of endotoxin, and is inhibited by the caspase-1 inhibitor YVADcmk but not by inhibitors of Fas-L, IL-1beta and IL-18. Importantly, the apoptosis inducing activity co-purifies with 100 nm sized microvesicles as determined by TEM of the pellets. These microvesicles contain caspase-1 and caspase-1 encapsulation is required since disruption of microvesicular integrity destroys the apoptotic activity but not the caspase-1 enzymatic activity. Thus, monocytes are capable of delivering a cell death message which depends upon the release of microvesicles containing functional caspase-1. This transcellular apoptosis induction pathway describes a novel pathway for inflammation induced programmed cell death.
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TWIST1 associates with NF-?B subunit RELA via carboxyl-terminal WR domain to promote cell autonomous invasion through IL8 production.
BMC Biol.
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Metastasis is the primary cause of death for cancer patients. TWIST1, an evolutionarily conserved basic helix-loop-helix (bHLH) transcription factor, is a strong promoter of metastatic spread and its expression is elevated in many advanced human carcinomas. However, the molecular events triggered by TWIST1 to motivate dissemination of cancer cells are largely unknown.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.