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Ziwei Zhang - One of the best experts on this subject based on the ideXlab platform.
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overexpression of nlrp3 nlrc4 and aim2 inflammasomes and their priming associated molecules tlr2 tlr4 dectin 1 dectin 2 and nfκb in malassezia folliculitis
Mycoses, 2018Co-Authors: Ni Liang, Yayun Wu, Yanping Yang, Wei Li, Ziwei ZhangAbstract:Background The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. Objectives To determine expression of four canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Methods Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1, and IL-1β mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls. Results Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB expression was upregulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P 0.05). qRT-PCR showed that levels of NLRP3, Casp-1, and IL-1β mRNA were significantly increased (P 0.05). Conclusions Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF. This article is protected by copyright. All rights reserved.
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Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming‐associated molecules (TLR2, TLR4, Dectin‐1, Dectin‐2 and NFκB) in Malassezia folliculitis
Mycoses, 2017Co-Authors: Ni Liang, Yayun Wu, Yanping Yang, Wei Li, Ziwei ZhangAbstract:Background The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. Objectives To determine expression of four canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Methods Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1, and IL-1β mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls. Results Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB expression was upregulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P 0.05). qRT-PCR showed that levels of NLRP3, Casp-1, and IL-1β mRNA were significantly increased (P 0.05). Conclusions Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF. This article is protected by copyright. All rights reserved.
Alessandra Pontillo - One of the best experts on this subject based on the ideXlab platform.
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Differential expression of the inflammasome complex genes in systemic lupus erythematosus
Immunogenetics, 2020Co-Authors: Heidi Lacerda Alves Cruz, Thiago Sotero Fragoso, Catarina Addobbati Jordão Cavalcanti, Camilla Albertina Dantas Lima, Alexandre Domingues Barbosa, Andréa Tavares Dantas, Henrique Mariz, Angela Luzia Branco Pinto Duarte, Jaqueline De Azevêdo Silva, Alessandra PontilloAbstract:Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving heterogeneous clinical manifestations and numerous susceptibility genes. Several findings evidence the critical role of inflammasomes in the predisposition to autoimmune diseases and in SLE. We investigated whether inflammasome polymorphins could affect susceptibility to develop and/or severity SLE. Moreover, differences in inflammasome activation in peripheral blood were also evaluated in SLE patients and controls. The distribution of 13 SNPs in eight inflammasome genes was evaluated. To assess inflammasome priming in peripheral blood monocytes of SLE and controls, differential expression of selected inflammasome genes and IL-1ß production was analyzed in resting condition as well as after LPS and ATP stimulation. Results showed that the gain-of-function variant rs10754558 ( NLRP3) was significantly more frequent in SLE patients with nephritis, reinforcing the concept of a key role of NLRP3 inflammasome not only in SLE but also especially in kidney disease. SLE monocytes in resting condition showed a higher level of IL-1ß expression and produced higher levels of IL-1ß when stimulated with LPS+ATP comparing to controls. The stimulation induced a significant expression of NLRP1 , AIM2 , CASP1 , and IL1B genes, suggesting that the NLRP1 inflammasome is responsible for the IL-1ß production observed in monocytes. These data emphasized once more the important contribution of inflammasome in SLE-associated inflammation.
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NLRP1 l155h polymorphism is a risk factor for preeclampsia development
American Journal of Reproductive Immunology, 2015Co-Authors: Alessandra Pontillo, Edione C Reis, Pamela N Bricher, Priscila Vianna, Solange Diniz, Karla Fernandes, Jose Artur Bogo Chies, Valeria C SandrimAbstract:Problem Augmented levels of IL-1s have been pointed out as an important pathogenic factor for preeclampsia development. Inflammasome is the cytoplasmic complex responsible for pro-IL1s cleavage and IL-1s secretion. Aim of the study was to evaluate the association between polymorphisms in inflammasome' genes and preeclampsia. Method of study Selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, and IL1B) were analyzed in 286 Brazilian women with and 309 without preeclampsia. Results and Conlclusions The NLRP1 variant rs12150220 (L155H) was associated with the development of preeclampsia (OR = 1.58), suggesting a role of this inflammasome receptor in the pathogenesis of this multifactorial disorder.
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NLRP1 haplotypes associated with leprosy in brazilian patients
Infection Genetics and Evolution, 2013Co-Authors: Alessandra Pontillo, Sergio Crovella, Weber Laurentino, Ana Carla PereiraAbstract:Abstract Polymorphisms in innate immunity genes are known to be involved in the multifactorial susceptibility to Mycobacterium leprae infection. M. leprae can downregulate IL-1β secretion escaping monocyte digestion. The intracellular receptors NLRPs (NACHT, LRR and PYD domains-containing proteins) sense pathogen associated molecular patterns (PAMPs) activating caspase-1 and IL-1β secretion in the context of inflammasome. Considering the possible role of inflammasome in the immune response against M. leprae, known single nucleotide polymorphisms (SNPs) in two NLRP genes, NLRP1 and NLRP3, were analyzed in Brazilian leprosy patients. Disease-associated SNPs (5 in NLRP1 and 2 in NLRP3), previously associated to infections and to immunologic disorders, were genotyped in 467 leprosy patients (327 multibacillary, MB; 96 paucibacillary, PB) and in 380 healthy controls (HC) from the state of Sao Paulo (Brazil), and in 183 patients (147 MB; 64 PB) and 186 HC from Mato Grosso (Brazil). Logistic regression analysis was performed considering susceptibility to leprosy di per se (leprosy versus HC) and clinical form (MB versus PB), adjusting for gender and ethnicity. Whereas none of the considered SNPs were statistically associated with leprosy, the NLRP1 combined haplotype rs2137722/G-rs12150220/T-rs2670660/G resulted significantly more frequent in patients than in HC as well as in PB than in MB. While both associations were lost after correction for gender and ethnicity, the NLRP1 combined haplotype rs2137722/G-rs12150220/A-rs2670660/G resulted strongly associated to PB. NLRP1 might be involved in the susceptibility to leprosy with particular emphasis for PB clinical form. Although preliminary, this is the first report linking NLRPs and inflammasome with leprosy: replication studies as well as functional assays are envisaged to deeper investigate the role of NLRP1 in M. leprae infection. Interestingly, NLRP1 SNPs were previously associated to susceptibility to Crohn disease, suggesting that NLRP1 could be a new modifier gene in common between leprosy and Crohn disease.
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the missense variation q705k in cias1 nalp3 nlrp3 gene and an NLRP1 haplotype are associated with celiac disease
The American Journal of Gastroenterology, 2011Co-Authors: Alessandra Pontillo, Anna Vendramin, Eulalia Catamo, Annalisa Fabris, Sergio CrovellaAbstract:OBJECTIVES: Celiac disease (CD) is a multifactorial common disorder with several susceptibility loci. Variations in the NALP1/NLRP1 and NALP3/NLRP3 genes have been reported to confer risk for several autoimmune conditions. We hypothesized that polymorphisms in these genes, due to their role in innate immunity and inflammatory processes, may affect susceptibility to CD. METHODS: Two single-nucleotide polymorphisms (SNPs) in NLRP1 (rs12150220, rs2670660) and two SNPs (rs10754558, rs35829419) in NLRP3 genes were genotyped in 504 CD Italian patients and 256 healthy controls. RESULTS: The minor A allele of NLRP3 rs35829419 (Q705K) polymorphism appeared to exert a protective role against the development of CD (P=0.029; odds ratio (OR)=0.56). Moreover, a particular NLRP1 haplotype was associated with predisposition to CD (P=0.003; OR=1.38), even more when present in combination with the rs35829419 major C allele (P=0.002; OR=1.42). CONCLUSIONS: We hypothesized that the deregulation of CIAS1/NALP3/NLRP3 and NALP1/NLRP1 inflammasomes could have a role in CD pathogenesis.
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The missense variation Q705K in CIAS1/NALP3/NLRP3 gene and an NLRP1 haplotype are associated with celiac disease.
The American Journal of Gastroenterology, 2011Co-Authors: Alessandra Pontillo, Anna Vendramin, Eulalia Catamo, Annalisa Fabris, Sergio CrovellaAbstract:OBJECTIVES: Celiac disease (CD) is a multifactorial common disorder with several susceptibility loci. Variations in the NALP1/NLRP1 and NALP3/NLRP3 genes have been reported to confer risk for several autoimmune conditions. We hypothesized that polymorphisms in these genes, due to their role in innate immunity and inflammatory processes, may affect susceptibility to CD. METHODS: Two single-nucleotide polymorphisms (SNPs) in NLRP1 (rs12150220, rs2670660) and two SNPs (rs10754558, rs35829419) in NLRP3 genes were genotyped in 504 CD Italian patients and 256 healthy controls. RESULTS: The minor A allele of NLRP3 rs35829419 (Q705K) polymorphism appeared to exert a protective role against the development of CD (P=0.029; odds ratio (OR)=0.56). Moreover, a particular NLRP1 haplotype was associated with predisposition to CD (P=0.003; OR=1.38), even more when present in combination with the rs35829419 major C allele (P=0.002; OR=1.42). CONCLUSIONS: We hypothesized that the deregulation of CIAS1/NALP3/NLRP3 and NALP1/NLRP1 inflammasomes could have a role in CD pathogenesis.
Mahtab Moayeri - One of the best experts on this subject based on the ideXlab platform.
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frontline science anthrax lethal toxin induced NLRP1 mediated il 1β release is a neutrophil and pad4 dependent event
Journal of Leukocyte Biology, 2020Co-Authors: Allison J Greaney, Devorah Crown, Stephen H. Leppla, Makayla K Portley, Danielle Omard, Nolan K Maier, Megan A Mendenhall, Katrin D Mayerbarber, Mahtab MoayeriAbstract:: Anthrax lethal toxin (LT) is a protease that activates the NLRP1b inflammasome sensor in certain rodent strains. Unlike better-studied sensors, relatively little is known about the priming requirements for NLRP1b. In this study, we investigate the rapid and striking priming-independent LT-induced release of IL-1β in mice within hours of toxin challenge. We find IL-1β release to be a NLRP1b- and caspase-1-dependent, NLRP3 and caspase-11-independent event that requires both neutrophils and peptidyl arginine deiminiase-4 (PAD4) activity. The simultaneous LT-induced IL-18 response is neutrophil-independent. Bone marrow reconstitution experiments in mice show toxin-induced IL-1β originates from hematopoietic cells. LT treatment of neutrophils in vitro did not induce IL-1β, neutrophil extracellular traps (NETs), or pyroptosis. Although platelets interact closely with neutrophils and are also a potential source of IL-1β, they were unable to bind or endocytose LT and did not secrete IL-1β in response to the toxin. LT-treated mice had higher levels of cell-free DNA and HMGB1 in circulation than PBS-treated controls, and treatment of mice with recombinant DNase reduced the neutrophil- and NLRP1-dependent IL-1β release. DNA sensor AIM2 deficiency, however, did not impact IL-1β release. These data, in combination with the findings on PAD4, suggest a possible role for in vivo NETs or cell-free DNA in cytokine induction in response to LT challenge. Our findings suggest a complex interaction of events and/or mediators in LT-treated mice with the neutrophil as a central player in induction of a profound and rapid inflammatory response to toxin.
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the cyclopentenone prostaglandin 15d pgj2 inhibits the NLRP1 and nlrp3 inflammasomes
Journal of Immunology, 2015Co-Authors: Nolan K Maier, Stephen H. Leppla, Mahtab MoayeriAbstract:Inflammasomes are cytosolic protein complexes that respond to diverse danger signals by activating caspase-1. The sensor components of the inflammasome, often proteins of the nucleotide-binding oligomerization domain–like receptor (NLR) family, detect stress, danger stimuli, and pathogen-associated molecular patterns. We report that the eicosanoid 15-deoxy-Δ12,14–PGJ2 (15d-PGJ2) and related cyclopentenone PGs inhibit caspase-1 activation by the NLR family leucine-rich repeat protein (NLRP)1 and NLRP3 inflammasomes. This inhibition was independent of the well-characterized role of 15d-PGJ2 as a peroxisome proliferator receptor-γ agonist, its activation of NF erythroid 2–related factor 2, or its anti-inflammatory function as an inhibitor of NF-κB. Instead, 15d-PGJ2 prevents the autoproteolytic activation of caspase-1 and the maturation of IL-1β through induction of a cellular state inhibitory to caspase-1 proteolytic function. The eicosanoid does not directly modify or inactivate the caspase-1 enzyme. Rather, inhibition is dependent on de novo protein synthesis. In a mouse peritonitis model of gout, using monosodium urate crystals to activate NLRP3, 15d-PGJ2 caused a significant inhibition of cell recruitment and associated IL-1β release. Furthermore, in a murine anthrax infection model, 15d-PGJ2 reversed anthrax lethal toxin-mediated NLRP1-dependent resistance. The findings reported in this study suggest a novel mechanism for the anti-inflammatory properties of the cyclopentenone PGs through inhibition of caspase-1 and the inflammasome.
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arsenic trioxide and other arsenical compounds inhibit the NLRP1 nlrp3 and naip5 nlrc4 inflammasomes
Journal of Immunology, 2014Co-Authors: Nolan Maier, Devorah Crown, Stephen H. Leppla, Mahtab MoayeriAbstract:Inflammasomes are large cytoplasmic multiprotein complexes that activate caspase-1 in response to diverse intracellular danger signals. Inflammasome components termed nucleotide-binding oligomerization domain–like receptor (NLR) proteins act as sensors for pathogen-associated molecular patterns, stress, or danger stimuli. We discovered that arsenicals, including arsenic trioxide and sodium arsenite, inhibited activation of the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes by their respective activating signals, anthrax lethal toxin, nigericin, and flagellin. These compounds prevented the autoproteolytic activation of caspase-1 and the processing and secretion of IL-1β from macrophages. Inhibition was independent of protein synthesis induction, proteasome-mediated protein breakdown, or kinase signaling pathways. Arsenic trioxide and sodium arsenite did not directly modify or inhibit the activity of preactivated recombinant caspase-1. Rather, they induced a cellular state inhibitory to both the autoproteolytic and substrate cleavage activities of caspase-1, which was reversed by the reactive oxygen species scavenger N -acetylcysteine but not by reducing agents or NO pathway inhibitors. Arsenicals provided protection against NLRP1-dependent anthrax lethal toxin–mediated cell death and prevented NLRP3-dependent neutrophil recruitment in a monosodium urate crystal inflammatory murine peritonitis model. These findings suggest a novel role in inhibition of the innate immune response for arsenical compounds that have been used as therapeutics for a few hundred years.
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transcriptional analysis of the three NLRP1 paralogs in mice
BMC Genomics, 2013Co-Authors: Inka Sastalla, Devorah Crown, Stephen H. Leppla, Seth L Masters, Andrew Mckenzie, Mahtab MoayeriAbstract:Background Signals of danger and damage in the cytosol of cells are sensed by NOD-like receptors (NLRs), which are components of multiprotein complexes called inflammasomes. Inflammasomes activate caspase-1, resulting in IL-1-beta and IL-18 secretion and an inflammatory response. To date, the only known activator of rodent NLRP1 is anthrax lethal toxin (LT), a protease secreted by the bacterial pathogen Bacillus anthracis. Although susceptibility of mouse macrophages to LT has been genetically linked to NLRP1b, mice harbor two additional NLRP1 paralogs in their genomes (NLRP1a and NLRP1c). However, little is known about their expression profile and sequence in different mouse strains. Furthermore, simultaneous expression of these paralogs may lead to competitional binding of NLRP1b interaction partners needed for inflammasome activation, thus influencing macrophages susceptibility to LT. To more completely understand the role(s) of NLRP1 paralogs in mice, we surveyed for their expression in a large set of LT-resistant and sensitive mouse macrophages. In addition, we provide sequence comparisons for NLRP1a and report on previously unrecognized splice variants of NLRP1b.
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anthrax lethal factor cleavage of NLRP1 is required for activation of the inflammasome
PLOS Pathogens, 2012Co-Authors: Jonathan L Levinsohn, Zachary L Newman, Kristina A Hellmich, Rasem J Fattah, Matthew A Getz, Inka Sastalla, Stephen H. Leppla, Mahtab MoayeriAbstract:NOD-like receptor (NLR) proteins (Nlrps) are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. Their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis) and maturation of IL-1β and IL-18. Anthrax lethal toxin (LT) induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from certain inbred rodent strains through activation of the NOD-like receptor (NLR) NLRP1 inflammasome. Here we show that LT cleaves rat NLRP1 and this cleavage is required for toxin-induced inflammasome activation, IL-1 β release, and macrophage pyroptosis. These results identify both a previously unrecognized mechanism of activation of an NLR and a new, physiologically relevant protein substrate of LT.
Sergio Crovella - One of the best experts on this subject based on the ideXlab platform.
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NLRP1 and nlrp3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population based autopsy study from north east italy
Infectious Agents and Cancer, 2015Co-Authors: Violetta Borelli, Sergio Crovella, Ronald Moura, Elisa TrevisanAbstract:NRLP1 (rs12150220, rs9889625, rs9900356, rs6502867, rs2670660) and NLRP3 (rs35829419, rs10754558) polymorphisms have been analyzed in 69 subjects with documented asbestos exposure and death for malignant pleural mesothelioma and 59 patients with documented asbestos exposure but death for other causes, all from a North East Italy. No association was found between NLRP1 and NLRP3 polymorphisms and susceptibility to develop mesothelioma using the general, dominant or recessive models. Also haplotype analysis did not reveal any significant association with mesothelioma. Our findings, being controversial with respect to another study on Italian patients, do suggest the need of further studies to unravel the contribution of NLRP1 and NLRP3 in susceptibility to mesothelioma.
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NLRP1 haplotypes associated with leprosy in brazilian patients
Infection Genetics and Evolution, 2013Co-Authors: Alessandra Pontillo, Sergio Crovella, Weber Laurentino, Ana Carla PereiraAbstract:Abstract Polymorphisms in innate immunity genes are known to be involved in the multifactorial susceptibility to Mycobacterium leprae infection. M. leprae can downregulate IL-1β secretion escaping monocyte digestion. The intracellular receptors NLRPs (NACHT, LRR and PYD domains-containing proteins) sense pathogen associated molecular patterns (PAMPs) activating caspase-1 and IL-1β secretion in the context of inflammasome. Considering the possible role of inflammasome in the immune response against M. leprae, known single nucleotide polymorphisms (SNPs) in two NLRP genes, NLRP1 and NLRP3, were analyzed in Brazilian leprosy patients. Disease-associated SNPs (5 in NLRP1 and 2 in NLRP3), previously associated to infections and to immunologic disorders, were genotyped in 467 leprosy patients (327 multibacillary, MB; 96 paucibacillary, PB) and in 380 healthy controls (HC) from the state of Sao Paulo (Brazil), and in 183 patients (147 MB; 64 PB) and 186 HC from Mato Grosso (Brazil). Logistic regression analysis was performed considering susceptibility to leprosy di per se (leprosy versus HC) and clinical form (MB versus PB), adjusting for gender and ethnicity. Whereas none of the considered SNPs were statistically associated with leprosy, the NLRP1 combined haplotype rs2137722/G-rs12150220/T-rs2670660/G resulted significantly more frequent in patients than in HC as well as in PB than in MB. While both associations were lost after correction for gender and ethnicity, the NLRP1 combined haplotype rs2137722/G-rs12150220/A-rs2670660/G resulted strongly associated to PB. NLRP1 might be involved in the susceptibility to leprosy with particular emphasis for PB clinical form. Although preliminary, this is the first report linking NLRPs and inflammasome with leprosy: replication studies as well as functional assays are envisaged to deeper investigate the role of NLRP1 in M. leprae infection. Interestingly, NLRP1 SNPs were previously associated to susceptibility to Crohn disease, suggesting that NLRP1 could be a new modifier gene in common between leprosy and Crohn disease.
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NLRP1 polymorphisms in patients with asbestos-associated mesothelioma
Infectious Agents and Cancer, 2012Co-Authors: Martina Girardelli, Sergio Crovella, Iva Maestri, Rosa Rinaldi, Mauro Tognon, Renzo Boldorini, Massimo Bovenzi, Manola ComarAbstract:Background: An increasing incidence of malignant mesothelioma (MM) cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin (IL)-1 beta (s) activated within the inflammasome complex. NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1s secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival/apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM. Methods: 134 Italian patients with diagnosis of mesothelioma due (MMAE, n=69) or not (MMAF, n=65) to asbestos, 256 healthy Italian blood donors and 101 Italian healthy subjects exposed to asbestos (HCAE) were genotyped for NLRP1 (rs2670660 and rs12150220) and NLRP3 (rs35829419 and rs10754558) polymorphisms. Results: While NLRP3 SNPs were not associated to mesothelioma, the NLRP1 rs12150220 allele T was significantly more frequent in MMAE (0.55) than in HCAE (0.41) (p=0.011; OR=1.79) suggesting a predisponent effect of this allele on the development of mesothelioma. This effect was amplified when the NLRP1 rs2670660 allele was combined with the NLRP1 rs12150220 allele (p=0.004; OR=0.52). Conclusion: Although NLRP3 SNPs was not involved in mesothelioma predisposition, these data proposed NLRP1 as a novel factor possibly involved in the development of mesothelioma.
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NLRP1 polymorphisms in patients with asbestos associated mesothelioma
Infectious Agents and Cancer, 2012Co-Authors: Martina Girardelli, Sergio Crovella, Iva Maestri, Rosa Rinaldi, Mauro Tognon, Renzo Boldorini, Massimo Bovenzi, Manola ComarAbstract:Background An increasing incidence of malignant mesothelioma (MM) cases in patients with low levels of asbestos exposure suggests the interference of alternative cofactors. SV40 infection was detected, as co-morbidity factor, only in 22% of asbestos-MM patients from a North-Eastern Italy area. An additional mechanism of injury related to asbestos exposure in MM development has been recently associated to inflammatory responses, principally driven by interleukin (IL)-1 beta (s) activated within the inflammasome complex. NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1s secretion while NLRP1 is expressed in lung epithelial cells and alveolar macrophages and contributes to the immune response and to survival/apoptosis balance. This study proposes to evaluate the impact of known NLRP3 and NLRP1 polymorphisms in the individual susceptibility to asbestos-induced mesothelioma in subjects from a hyperendemic area for MM.
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the missense variation q705k in cias1 nalp3 nlrp3 gene and an NLRP1 haplotype are associated with celiac disease
The American Journal of Gastroenterology, 2011Co-Authors: Alessandra Pontillo, Anna Vendramin, Eulalia Catamo, Annalisa Fabris, Sergio CrovellaAbstract:OBJECTIVES: Celiac disease (CD) is a multifactorial common disorder with several susceptibility loci. Variations in the NALP1/NLRP1 and NALP3/NLRP3 genes have been reported to confer risk for several autoimmune conditions. We hypothesized that polymorphisms in these genes, due to their role in innate immunity and inflammatory processes, may affect susceptibility to CD. METHODS: Two single-nucleotide polymorphisms (SNPs) in NLRP1 (rs12150220, rs2670660) and two SNPs (rs10754558, rs35829419) in NLRP3 genes were genotyped in 504 CD Italian patients and 256 healthy controls. RESULTS: The minor A allele of NLRP3 rs35829419 (Q705K) polymorphism appeared to exert a protective role against the development of CD (P=0.029; odds ratio (OR)=0.56). Moreover, a particular NLRP1 haplotype was associated with predisposition to CD (P=0.003; OR=1.38), even more when present in combination with the rs35829419 major C allele (P=0.002; OR=1.42). CONCLUSIONS: We hypothesized that the deregulation of CIAS1/NALP3/NLRP3 and NALP1/NLRP1 inflammasomes could have a role in CD pathogenesis.
Ni Liang - One of the best experts on this subject based on the ideXlab platform.
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overexpression of nlrp3 nlrc4 and aim2 inflammasomes and their priming associated molecules tlr2 tlr4 dectin 1 dectin 2 and nfκb in malassezia folliculitis
Mycoses, 2018Co-Authors: Ni Liang, Yayun Wu, Yanping Yang, Wei Li, Ziwei ZhangAbstract:Background The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. Objectives To determine expression of four canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Methods Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1, and IL-1β mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls. Results Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB expression was upregulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P 0.05). qRT-PCR showed that levels of NLRP3, Casp-1, and IL-1β mRNA were significantly increased (P 0.05). Conclusions Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF. This article is protected by copyright. All rights reserved.
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Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming‐associated molecules (TLR2, TLR4, Dectin‐1, Dectin‐2 and NFκB) in Malassezia folliculitis
Mycoses, 2017Co-Authors: Ni Liang, Yayun Wu, Yanping Yang, Wei Li, Ziwei ZhangAbstract:Background The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. Objectives To determine expression of four canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Methods Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1, and IL-1β mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls. Results Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2, and NFκB expression was upregulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P 0.05). qRT-PCR showed that levels of NLRP3, Casp-1, and IL-1β mRNA were significantly increased (P 0.05). Conclusions Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF. This article is protected by copyright. All rights reserved.