The Experts below are selected from a list of 1443 Experts worldwide ranked by ideXlab platform
Jürg Tschopp - One of the best experts on this subject based on the ideXlab platform.
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The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
Molecular Cell, 2002Co-Authors: Fabio Martinon, Kimberly Burns, Jürg TschoppAbstract:Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, PYCARD/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of PYCARD. Moreover, expression of a dominant-negative form of PYCARD in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
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The Inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-β
Molecular Cell, 2002Co-Authors: Fabio Martinon, Kimberly Burns, Jürg TschoppAbstract:Generation of Interleukin (IL)-1β via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, PYCARD/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1β processing is lost upon prior immunodepletion of PYCARD. Moreover, expression of a dominant-negative form of PYCARD in differentiated THP-1 cells blocks proIL-1β maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
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the inflammasome a molecular platform triggering activation of inflammatory caspases and processing of proil beta
Molecular Cell, 2002Co-Authors: Fabio Martinon, Kimberly Burns, Jürg TschoppAbstract:Abstract Generation of Interleukin (IL)-1β via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, PYCARD/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1β processing is lost upon prior immunodepletion of PYCARD. Moreover, expression of a dominant-negative form of PYCARD in differentiated THP-1 cells blocks proIL-1β maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
željko Debeljak - One of the best experts on this subject based on the ideXlab platform.
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promoter methylation status of asc tms1 PYCARD is associated with decreased overall survival and tnm status in patients with early stage non small cell lung cancer nsclc
Translational lung cancer research, 2019Co-Authors: Maja Sutic, Antje Motzek, Gordana Bubanovic, Matthias Linke, Ivan Sabol, Oliver Vugrek, Petar Ozretic, Luka Brcic, Sven Seiwerth, željko DebeljakAbstract:Background: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. Methods: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Meth- ylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non-malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver-operating characteristics (ROC) analysis and statistical tests of hypothesis. Results: Methylation level of tested genes is generally low but significantly decreased in tumor tissues ( ASC/ TMS1/PYCARD , P MyD88 , P ASC/TMS1/ PYCARD and CpG1 (-253 position) and 2 (-265 position) in MyD88 . The association study showed that the methylation status of the ASC/TMS1 CpG4 site (-34 position) in malignant and non-malignant tissues is associated with the overall survival (P=0.019) and the methylation status of CpG8 site (-92 position) is associ- ated with TNM-stage (P=0.011). Conclusions: The methylation status of the ASC/TMS1/PYCARD and MyD88 promoters are promising prognostic biomarker candidates. However, presented results should be considered as a preliminary and should be confirmed on the larger number of the samples.
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Promoter methylation status of ASC/TMS1/PYCARD is associated with decreased overall survival and TNM status in patients with early stage non-small cell lung cancer (NSCLC)
Translational lung cancer research, 2019Co-Authors: Maja Šutić, Antje Motzek, Matthias Linke, Ivan Sabol, Oliver Vugrek, Sven Seiwerth, Gordana Bubanović, Petar Ozretić, Luka Brčić, željko DebeljakAbstract:Background: Lung cancer is the leading cause of cancer-related death worldwide, with 5-year overall survival less than 15%. Therefore, it is essential to find biomarkers for early detection and prognosis. Aberrant DNA methylation is a common feature of human cancers and its utility is already recognized in cancer management. The aim of this study was to explore the diagnostic and prognostic value of the promoter methylation status of the ASC/TMS1/PYCARD and MyD88 genes, key adaptor molecules in the activation of the innate immune response and apoptosis pathways. Methods: A total of 50 non-small cell lung cancer (NSCLC) patients were enrolled in the study. Meth- ylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen malignant tissues and adjacent non-malignant tissues. Associations between methylation and lung function, tumor grade and overall survival were evaluated using receiver-operating characteristics (ROC) analysis and statistical tests of hypothesis. Results: Methylation level of tested genes is generally low but significantly decreased in tumor tissues ( ASC/ TMS1/PYCARD , P MyD88 , P ASC/TMS1/ PYCARD and CpG1 (-253 position) and 2 (-265 position) in MyD88 . The association study showed that the methylation status of the ASC/TMS1 CpG4 site (-34 position) in malignant and non-malignant tissues is associated with the overall survival (P=0.019) and the methylation status of CpG8 site (-92 position) is associ- ated with TNM-stage (P=0.011). Conclusions: The methylation status of the ASC/TMS1/PYCARD and MyD88 promoters are promising prognostic biomarker candidates. However, presented results should be considered as a preliminary and should be confirmed on the larger number of the samples.
Fabio Martinon - One of the best experts on this subject based on the ideXlab platform.
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The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
Molecular Cell, 2002Co-Authors: Fabio Martinon, Kimberly Burns, Jürg TschoppAbstract:Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, PYCARD/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of PYCARD. Moreover, expression of a dominant-negative form of PYCARD in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
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The Inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-β
Molecular Cell, 2002Co-Authors: Fabio Martinon, Kimberly Burns, Jürg TschoppAbstract:Generation of Interleukin (IL)-1β via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, PYCARD/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1β processing is lost upon prior immunodepletion of PYCARD. Moreover, expression of a dominant-negative form of PYCARD in differentiated THP-1 cells blocks proIL-1β maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
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the inflammasome a molecular platform triggering activation of inflammatory caspases and processing of proil beta
Molecular Cell, 2002Co-Authors: Fabio Martinon, Kimberly Burns, Jürg TschoppAbstract:Abstract Generation of Interleukin (IL)-1β via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, PYCARD/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1β processing is lost upon prior immunodepletion of PYCARD. Moreover, expression of a dominant-negative form of PYCARD in differentiated THP-1 cells blocks proIL-1β maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
Jingguo Zhou - One of the best experts on this subject based on the ideXlab platform.
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Changes in expression of PYCARD gene and its transcript variant mRNA in peripheral blood mononuclear cells of patients with primary gout
Journal of Sichuan University. Medical science edition, 2020Co-Authors: Wantai Dang, Mingcai Zhao, Hong Jiang, Lingqin Li, Chang Zhou, Jingguo ZhouAbstract:OBJECTIVE: To determine the expression level and role of PYCARD [PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase recruitment domain (CARD), PYCARD] gene and its transcript variant mRNA in peripheral blood mononuclear cells (PBMCs) of patients with primary gout (PG). METHODS: PYCARD gene and its transcript variant mRNA were measured using reverse transcription-polymerase chain reaction (RT-PCR) in PBMCs. The expression of PYCARD gene and PYCARD-1,-2 mRNA in PBMCs was compared between the patients with acute phase PG (APPG) (n=44), non-acute phase PG (NAPPG) (n= 51) and healthy controls (HC) (n=87). PYCARD and NF-kappaB (p105/p50) protein expressions were measured using Western blot in the PBMCs of participants in the PG and HC groups. Routine blood tests and blood uric acid test were undertaken in all participants. Differences in the indicators were examined among the three groups. Correlations between the expression of PYCARD gene and PYCARD-1,-2 mRNA and other indicators were analyzed. RESULTS: The expression level of PYCARD gene, PYCARD-1,-2 mRNA was significantly higher in the APPG and NAPPG group than in the HC group (P
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expression of PYCARD gene transcript variant mrna in peripheral blood mononuclear cells of primary gout patients with different chinese medicine syndromes
Chinese Journal of Integrative Medicine, 2018Co-Authors: Wantai Dang, Jingguo ZhouAbstract:Objective To study the expression level and role of apoptosis-associated speck-like protein containing a caspase recruitment domain (PYCARD) gene transcript variant mRNA in peripheral blood mononuclear cells (PBMCs) of primary gout (PG) patients with different Chinese medicine (CM) syndromes.
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changes in expression of PYCARD gene and its transcript variant mrna in peripheral blood mononuclear cells of patients with primary gout
Journal of Sichuan University. Medical science edition, 2015Co-Authors: Wantai Dang, Mingcai Zhao, Hong Jiang, Lingqin Li, Chang Zhou, Jingguo ZhouAbstract:OBJECTIVE: To determine the expression level and role of PYCARD [PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase recruitment domain (CARD), PYCARD] gene and its transcript variant mRNA in peripheral blood mononuclear cells (PBMCs) of patients with primary gout (PG). METHODS: PYCARD gene and its transcript variant mRNA were measured using reverse transcription-polymerase chain reaction (RT-PCR) in PBMCs. The expression of PYCARD gene and PYCARD-1,-2 mRNA in PBMCs was compared between the patients with acute phase PG (APPG) (n=44), non-acute phase PG (NAPPG) (n= 51) and healthy controls (HC) (n=87). PYCARD and NF-kappaB (p105/p50) protein expressions were measured using Western blot in the PBMCs of participants in the PG and HC groups. Routine blood tests and blood uric acid test were undertaken in all participants. Differences in the indicators were examined among the three groups. Correlations between the expression of PYCARD gene and PYCARD-1,-2 mRNA and other indicators were analyzed. RESULTS: The expression level of PYCARD gene, PYCARD-1,-2 mRNA was significantly higher in the APPG and NAPPG group than in the HC group (P<0.01). The NAPPG group had significantly higher levels of PYCARD gene transcript variant 2x mRNA and 2y mRNA in the HC and APPG groups (P<0.05). The expression of PYCARD and NF-kappaB (p105/p50) protein was significantly higher in the PG group compared with the HC group [(4.900 +/- 1.324) vs. (3.975 +/- 0.210) and (0.263 +/- 0.106) vs. (0.127 +/- 0.008), respectively P<0.05]. The expression level of PYCARD-2 mRNA and granulocyte were positively correlated in the NAPPG group. CONCLUSION: Abnormal expression of PYCARD gene and its transcript variant and PYCARD protein in PG patients suggests that PYCARD gene and its transcript variant may play an important role in regulating the inflammatory response of PG patients.
Jenny P Y Ting - One of the best experts on this subject based on the ideXlab platform.
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granuloma formation and host defense in chronic mycobacterium tuberculosis infection requires PYCARD asc but not nlrp3 or caspase 1
PLOS ONE, 2010Co-Authors: Erin Mcelvania Tekippe, Irving C Allen, Paul Hulseberg, Jonathan Tabb Sullivan, Jessica R Mccann, Matyas Sandor, Miriam Braunstein, Jenny P Y TingAbstract:The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1β secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3−/−, Casp-1−/−, and WT mice showed no differences in pulmonary IL-1β production, bacterial burden, or long-term survival. In contrast, a significant role was observed for PYCARD in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of PYCARD−/− mice. Decreased survival of PYCARD−/− animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.
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Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1.
PLOS ONE, 2010Co-Authors: Erin Mcelvania Tekippe, Irving C Allen, Paul Hulseberg, Jonathan Tabb Sullivan, Jessica R Mccann, Matyas Sandor, Miriam Braunstein, Jenny P Y TingAbstract:The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1β secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3−/−, Casp-1−/−, and WT mice showed no differences in pulmonary IL-1β production, bacterial burden, or long-term survival. In contrast, a significant role was observed for PYCARD in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of PYCARD−/− mice. Decreased survival of PYCARD−/− animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.
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The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer
Journal of Experimental Medicine, 2010Co-Authors: Irving C Allen, Erin Mcelvania Tekippe, Rita Marie T Woodford, Joshua M. Uronis, Eda K. Holl, Arlin B. Rogers, Hans H Herfarth, Christian Jobin, Jenny P Y TingAbstract:Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1β and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3−/− mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3−/− mice than in PYCARD−/− or Casp1−/− animals. No significant differences were observed in disease progression or outcome in Nlrc4−/− mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC.
