Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytes

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Show simple item record Beckley, Amy J. Lan, Li-Qiong Aono, Shelly Wang, Lei Shi, Jishu N. 2013-07-15T13:25:47Z 2013-07-15T13:25:47Z 2013-07-15 2013-05-26
dc.description.abstract AIM: To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β (pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events. METHODS: All experiments were performed on fresh or overnight cultured human peripheral blood monocytes (PBMCs) that were isolated from healthy donors. PBMCs were activated by lipopolysaccharide (LPS) stimulation before being treated with Adenosine triphosphate (ATP, 1 mmol/L), human α-defensin-5 (HD-5, 50 μg/mL), and/or nigericin (Nig, 30 μmol/L). For each experiment, the culture supernatants were collected separately from the cells. Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL-1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies. RESULTS: We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation. In the presence of HD-5, this release of IL-1β, but not the processing of pro-IL-1β to IL-1β, was completely inhibited. Similarly, in the presence of HD-5, the release of IL-1β, but not the processing of IL-1β, was significantly inhibited from LPS-activated monocytes stimulated with Nig. Finally, we treated LPS-activated monocytes with ATP and Nig and collected the supernatants. We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes. Interestingly, and contrary to IL-1β processing and release, caspase-1 cleavage and release was not blocked by HD-5. All images are representative of three independent experiments. CONCLUSION: These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events. en_US
dc.language.iso en_US en_US
dc.relation.uri en_US
dc.subject Caspase-1 en_US
dc.subject Human defensin en_US
dc.subject Monocytes en_US
dc.subject Interleukin-1β en_US
dc.subject Inflammasome en_US
dc.title Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytes en_US
dc.type Article (publisher version) en_US 2013 en_US
dc.citation.doi 10.4331/wjbc.v4.i2.30 en_US
dc.citation.epage 34 en_US
dc.citation.issue 2 en_US
dc.citation.jtitle World Journal of Biological Chemistry en_US
dc.citation.spage 30 en_US
dc.citation.volume 4 en_US
dc.contributor.authoreid beckleya en_US
dc.contributor.authoreid leiwang en_US
dc.contributor.authoreid jshi en_US

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