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

World Journal of Biological Chemistry 2013年第2期4卷 30-34页

作者： amy J galliher-beckley Li-Qiong Lan Shelly Aono Lei Wang Jishu Shi Department of Anatomy and Physiology College of Veterinary MedicineKansas State University College of Life Sciences Sichuan University Department of Anatomy Physiologyand PharmacologyCollege of Veterinary MedicineAuburn University

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 ***:All experiments were performed on fresh or overnight cultured human peripheral blood monocytes(PBMCs) that were isolated from healthy *** 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 *** lysates and supernatants were both subject to immunoprecipitation with anti-IL1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β ***: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 *** the presence of HD-5,this release of IL-1β,but not the processing of pro-IL-1β to IL-1β,was completely ***,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 ***,we treated LPS-activated monocytes with ATP and Nig and collected the *** found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the ***,and contrary to IL-1β processing and release,caspase-1 cleavage and release was not blocked by *** images are representative of three independent ***: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.

关键词： Caspase-1 Human defensin Monocytes Interleukin-1β processing and release Inflammasome

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Montanide<sup>TM</sup>Gel01 ST Adjuvant Enhances PRRS Modified Live Vaccine Efficacy by Regulating Porcine Humoral and Cellular Immune Responses

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World Journal of Vaccines 2013年第1期3卷 1-9页

作者： Xiangdong Li amy galliher-beckley Jerome C. Nietfeld Kay S. Faaberg Jishu Shi Department of Anatomy and Physiology College of Veterinary Medicine Kansas State University Manhattan USA Department of Diagnostic Medicine and Pathobiology College of Veterinary Medicine Kansas State University Manhattan USA Virus and Prion Research Unit National Animal Disease Center United States Department of Agriculture Ames USA

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vaccines (MLV). In this study, we explored the efficacy and immunological mechanisms of protection of MontanideTM Gel01 ST (Gel01) adjuvanted modified live PRRSV vaccine in pigs challenged with two genetically distinct strains of PRRSV. Gel01-MLV reduced lymph node pathology scores in pigs challenged with VR-2332 (parental strain of MLV vaccine) but not that in pigs challenged with MN184A (heterologous strain), when compared to that in pigs vaccinated with un-adjuvanted MLV. Pigs vaccinated with Gel01-MLV had higher levels of PRRS-specific antibodies, as measured by IDEXX ELISA and virus neutralizing antibodies, after vaccination and VR-2332 challenge. In addition, pigs vaccinated with Gel01-MLV had decreased levels of IFN-γ, IL-10, and T-regulatory lymphocytes in the blood as compared to that in pigs vaccinated with MLV alone. Interestingly, we found that addition of Gel01 did not change the profile of other T lymphocyte populations after PRRSV challenge. These results demonstrate that the MLV adjuvanted with Gel01 provides enhanced protection against homologous PRRSV infection, possibly by regulating the production of PRRSV-specific antibodies and cytokines involved in the development of T-regulatory cells. Thus, Gel01 ST is a promising adjuvant that can be formulated with PRRSV MLV vaccines to reduce disease severity and tissue damage caused by PRRSV infection in pigs.

关键词： PRRSV MontanideTM Gel01 ST IFN-γ Adjuvant IL-10 Immune Response Vaccine

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