@article {7732, title = {NLRP1 and NLRP3 polymorphisms in mesothelioma patients and asbestos exposed individuals a population-based autopsy study from North East Italy.}, journal = {Infect Agent Cancer}, volume = {10}, year = {2015}, month = {2015}, pages = {26}, abstract = {

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.

}, issn = {1750-9378}, doi = {10.1186/s13027-015-0022-0}, author = {Borelli, Violetta and Moura, Ronal R and Trevisan, Elisa and Crovella, Sergio} } @article {3624, title = {NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection.}, journal = {Mem Inst Oswaldo Cruz}, volume = {109}, year = {2014}, month = {2014 Nov}, pages = {960-3}, abstract = {

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

}, keywords = {Adult, Brazil, Carrier Proteins, Female, Genetic Predisposition to Disease, HTLV-I Infections, Human T-lymphotropic virus 1, Humans, Inflammasomes, Interleukin-1, Male, Middle Aged, Polymorphism, Single Nucleotide, Protective Factors}, issn = {1678-8060}, author = {Kamada, Anselmo Jiro and Pontillo, Alessandra and Guimar{\~a}es, Rafael Lima and Loureiro, Paula and Crovella, Sergio and Brand{\~a}o, Lucas Andr{\'e} Cavalcanti} } @article {3603, title = {Non-classical MHC-I human leukocyte antigen (HLA-G) in hepatotropic viral infections and in hepatocellular carcinoma.}, journal = {Hum Immunol}, volume = {75}, year = {2014}, month = {2014 Dec}, pages = {1225-31}, abstract = {

The human leukocyte antigen (HLA)-G is a "nonclassical" major histocompatibility complex (MHC) class Ib gene, located at chromosome 6, in the 6p21.3 region. The HLA-G presents immunomodulatory functions essential in pregnancy for the tolerance of the semi-allogenic fetus, but an abnormal expression of HLA-G has been observed in numerous pathological conditions, such as tumors, autoimmune diseases and viral infections. In recent years, numerous studies have assessed the clinical relevance of HLA-G expression in different types of cancer: in general, a higher HLA-G expression correlates with a lower survival rate or a shorter disease-free survival. Altered expression of HLA-G has been found in both HCV and HBV infection, and some genetic polymorphisms have been associated with altered susceptibility/disease development for these infections, however, whether the biologic role of HLA-G in HCV and HBV infection is beneficial or hazardous, it is not completely clear. In the context of hepatocellular carcinoma, HLA-G has shown a potential diagnostic role, moreover a prognostic value in HCC patients has been also attributed to HLA-G molecules. We revise here the role of HLA-G in hepatotropic HBV/HCV infections and in hepatocellular carcinoma (HCC).

}, keywords = {Carcinoma, Hepatocellular, Female, Genetic Predisposition to Disease, Hepatitis B, Hepatitis C, HLA-G Antigens, Humans, Immune Tolerance, Liver Neoplasms, Polymorphism, Genetic, Pregnancy}, issn = {1879-1166}, doi = {10.1016/j.humimm.2014.09.019}, author = {Catamo, Eulalia and Zupin, Luisa and Crovella, Sergio and Celsi, Fulvio and Segat, Ludovica} } @article {3502, title = {Novel missense mutation in the NOD2 gene in a patient with early onset ulcerative colitis: causal or chance association?}, journal = {Int J Mol Sci}, volume = {15}, year = {2014}, month = {2014}, pages = {3834-41}, abstract = {

Deregulated immune response to gut microflora in genetically predisposed individuals is typical for inflammatory bowel diseases. It is reasonable to assume that genetic association with the disease will be more pronounced in subjects with early onset than adult onset. The nucleotide-binding oligomerization domain containing-2 gene, commonly involved in multifactorial risk of Crohn{\textquoteright}s disease, and interleukin 10 receptor genes, associated with rare forms of early onset inflammatory bowel diseases, were sequenced in an early onset patient. We identified a novel variant in the NOD2 gene (c.2857A > G p.K953E) and two already described missense variants in the IL10RA gene (S159G and G351R). The new NOD2 missense variant was examined in silico with two online bioinformatics tools to predict the potentially deleterious effects of the mutation. Although cumulative effect of these variations in the early onset of the disease can be only hypothesized, we demonstrated that family information and in silico studies can be used to predict association with the disease.

}, keywords = {Age of Onset, Amino Acid Sequence, Base Sequence, Child, Colitis, Ulcerative, Crohn Disease, DNA Mutational Analysis, Genetic Predisposition to Disease, Genotype, Humans, Interleukin-10 Receptor alpha Subunit, Interleukin-10 Receptor beta Subunit, Molecular Sequence Data, Mutation, Missense, Nod2 Signaling Adaptor Protein, Polymorphism, Single Nucleotide, Risk Factors, Sequence Homology, Amino Acid}, issn = {1422-0067}, doi = {10.3390/ijms15033834}, author = {Girardelli, Martina and Vuch, Josef and Tommasini, Alberto and Crovella, Sergio and Bianco, Anna Monica} } @article {1731, title = {NALP1/NLRP1 genetic variants are associated with Alzheimer disease.}, journal = {Alzheimer Dis Assoc Disord}, volume = {26}, year = {2012}, month = {2012 Jul-Sep}, pages = {277-81}, abstract = {

Alzheimer disease (AD) is a complex neurodegenerative disease. Genetic and molecular studies have confirmed that in the human brain, amyloid-β fibrils can induce, through the activation of NALP1 inflammosome, inflammatory and apoptotic responses involved in the pathogenesis of AD. Considering that AD pathogenesis is multifactorial, we hypothesized that NALP1/NLRP1 could be a susceptibility gene involved in the devolvement of the disease. The possible association between 9 selected polymorphisms in the NALP1/NLRP1 gene and AD was evaluated by comparing their frequency distribution in an Italian cohort of AD patients (AD, n = 276) and in a group of Italian sex-matched and age-matched healthy controls without dementia (HC, n = 266). Our study, evidences the association of 4 nonsynonymous polymorphisms in the NLRP1 gene (rs2137722, rs34733791, rs11657747, rs11651595) with AD. The major alleles of all 4 single nucleotide polymorphisms and the corresponding homozygote genotypes were more frequent in AD patients than in healthy controls, suggesting an association of these variants in the predisposition versus the development of the disease. These findings seem to support the previously reported role of NALP1 in neuronal damage, and provide evidence of an association between single nucleotide variations in the NLRP1 gene and AD.

}, keywords = {Adaptor Proteins, Signal Transducing, Aged, 80 and over, Alzheimer Disease, Apoptosis Regulatory Proteins, Female, Genetic Predisposition to Disease, Genotype, Humans, Italy, Male, Polymerase Chain Reaction, Polymorphism, Single Nucleotide}, issn = {1546-4156}, doi = {10.1097/WAD.0b013e318231a8ac}, author = {Pontillo, Alessandra and Catamo, Eulalia and Arosio, Beatrice and Mari, Daniela and Crovella, Sergio} } @article {1913, title = {New insights in the sugarcane transcriptome responding to drought stress as revealed by superSAGE.}, journal = {ScientificWorldJournal}, volume = {2012}, year = {2012}, month = {2012}, pages = {821062}, abstract = {

In the scope of the present work, four SuperSAGE libraries have been generated, using bulked root tissues from four drought-tolerant accessions as compared with four bulked sensitive genotypes, aiming to generate a panel of differentially expressed stress-responsive genes. Both groups were submitted to 24 hours of water deficit stress. The SuperSAGE libraries produced 8,787,315 tags (26 bp) that, after exclusion of singlets, allowed the identification of 205,975 unitags. Most relevant BlastN matches comprised 567,420 tags, regarding 75,404 unitags with 164,860 different ESTs. To optimize the annotation efficiency, the Gene Ontology (GO) categorization was carried out for 186,191 ESTs (BlastN against Uniprot-SwissProt), permitting the categorization of 118,208 ESTs (63.5\%). In an attempt to elect a group of the best tags to be validated by RTqPCR, the GO categorization of the tag-related ESTs allowed the in silico identification of 213 upregulated unitags responding basically to abiotic stresses, from which 145 presented no hits after BlastN analysis, probably concerning new genes still uncovered in previous studies. The present report analyzes the sugarcane transcriptome under drought stress, using a combination of high-throughput transcriptome profiling by SuperSAGE with the Solexa sequencing technology, allowing the identification of potential target genes during the stress response.

}, keywords = {Droughts, Gene Expression Profiling, Heat-Shock Response, Plant Proteins, Saccharum, Transcriptome}, issn = {1537-744X}, doi = {10.1100/2012/821062}, author = {Kido, {\'E}derson Akio and Ferreira Neto, Jos{\'e} Ribamar Costa and Silva, Roberta Lane de Oliveira and Pandolfi, Valesca and Guimar{\~a}es, Ana Carolina Ribeiro and Veiga, Daniela Truffi and Chabregas, Sabrina Moutinho and Crovella, Sergio and Benko-Iseppon, Ana Maria} } @article {1971, title = {NLRP1 polymorphisms in patients with asbestos-associated mesothelioma.}, journal = {Infect Agent Cancer}, volume = {7}, year = {2012}, month = {2012}, pages = {25}, abstract = {

UNLABELLED:

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 ({\ss}) activated within the inflammasome complex.NLRP3 inflammosome has been described as the intracellular sensor for asbestos able to induce inflammasome activation and IL-1{\ss} 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.

}, issn = {1750-9378}, doi = {10.1186/1750-9378-7-25}, author = {Girardelli, Martina and Maestri, Iva and Rinaldi, Rosa R and Tognon, Mauro and Boldorini, Renzo and Bovenzi, Massimo and Crovella, Sergio and Comar, Manola} } @article {1674, title = {Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes.}, journal = {Int Immunopharmacol}, volume = {10}, year = {2010}, month = {2010 Jun}, pages = {639-42}, abstract = {

The inhibition of mevalonate pathway through genetic defects (mevalonate kinase deficiency, MKD) or pharmacologic drugs (aminobisphosphonates) causes a shortage of intermediate compounds and, in particular, of geranylgeranyl-pyrophosphate (GGPP) associated to the activation of caspase-1 and IL-1beta release. Geraniol (GOH), farnesol (FOH), geranylgeraniol (GGOH) and menthol (MOH), due to their isoprenoid structure, are supposed to enter the mevalonate pathway and to by-pass the biochemical block, reconstituting the pathway. Considering the already known side effects of aminobisphosphonates, and the lack of a specific treatment for MKD, we evaluated the impact of these natural isoprenoids compounds in a RAW cell lines chemically treated with the aminobisphosphonate alendronate, and in monocytes isolated from 2 patients affected by MKD. GOH, FOH, GGOH and MOH were all capable to diminish inflammatory marker levels induced by LPS. These natural isoprenoids could be proposed as novel therapeutic approach for the still orphan drug MKD, but also considered for the evaluation of possible inflammatory side effects of aminobisphosphonates.

}, keywords = {Animals, Cell Line, Cells, Cultured, Child, Child, Preschool, Cytokines, Diphosphonates, Humans, Inflammation, Interleukin-1beta, Lipopolysaccharides, Male, Mevalonate Kinase Deficiency, Mice, Monocytes, Nitric Oxide, Terpenes}, issn = {1878-1705}, doi = {10.1016/j.intimp.2010.03.008}, author = {Marcuzzi, Annalisa and Tommasini, Alberto and Crovella, Sergio and Pontillo, Alessandra} }