Publications by authors named "Francisca Vorraro"

8 Publications

  • Page 1 of 1

Trypanosoma cruzi infection in genetically selected mouse lines: genetic linkage with quantitative trait locus controlling antibody response.

Mediators Inflamm 2014 13;2014:952857. Epub 2014 Aug 13.

Laboratório de Imunogenética, Instituto Butantan, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.

Trypanosoma cruzi infection was studied in mouse lines selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reaction and for high (HIII) or low (LIII) antibody (Ab) responses to complex antigens. Resistance was associated with gender (females) and strain-the high responder lines AIRmax and HIII were resistant. The higher resistance of HIII as compared to LIII mice extended to higher infective doses and was correlated with enhanced production of IFN-γ and nitric oxide production by peritoneal and lymph node cells, in HIII males and females. We also analyzed the involvement of previously mapped Ab and T. cruzi response QTL with the survival of Selection III mice to T. cruzi infections in a segregating backcross [F1(HIII×LIII) ×LIII] population. An Ab production QTL marker mapping to mouse chromosome 1 (34.8 cM) significantly cosegregated with survival after acute T. cruzi infections, indicating that this region also harbors genes whose alleles modulate resistance to acute T. cruzi infection.
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http://dx.doi.org/10.1155/2014/952857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146349PMC
May 2015

Genetic control of IL-1 beta production and inflammatory response by the mouse Irm1 locus.

J Immunol 2010 Aug 7;185(3):1616-21. Epub 2010 Jul 7.

Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.

Genome-wide linkage analysis using single nucleotide polymorphism arrays was carried out in pedigrees of mice differing in the extent of acute inflammatory response (AIRmax or AIRmin). The AIR phenotype was determined by quantifying the number of infiltrating cells in the 24-h exudate induced by Biogel P-100 s.c. injection and by ex vivo IL-1beta production by leukocytes stimulated with LPS and ATP. We mapped the major inflammatory response modulator 1 locus on chromosome 7, at the 1-logarithm of odds (LOD) confidence interval from 116.75 to 139.75 Mb, linked to the number of infiltrating cells (LOD = 3.61) through the production of IL-1beta (LOD = 9.35). Of several interesting candidate genes mapping to the inflammatory response modulator 1 locus, 28 of these were differentially expressed in the bone marrow of AIRmax and AIRmin mice. These findings represent a step toward the identification of the genes underlying this complex phenotype.
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http://dx.doi.org/10.4049/jimmunol.1000358DOI Listing
August 2010

Genetic heterogeneity of inflammatory response and skin tumorigenesis in phenotypically selected mouse lines.

Cancer Lett 2010 Sep 21;295(1):54-8. Epub 2010 Mar 21.

Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Non-inbred AIR (AIRmax, AIRmin) and Car (Car-S, Car-R) mouse lines were generated from the same eight inbred mice through bidirectional selective breeding for acute inflammatory response and for susceptibility to two-stage skin tumorigenesis, respectively. Because AIR lines also showed a differential predisposition to skin tumorigenesis and Car lines differed in the extent of inflammatory response, we carried out genome-wide association studies using SNP arrays to identify the genetic elements affecting skin tumor susceptibility and inflammatory response in AIR and Car lines. We found that the phenotypic outcome reflects a specific genetic profile in each mouse line, suggesting that distinct genetic elements, selected by differential genetic drifts, and exerting pleiotropic effects in each mouse population, control the skin tumor susceptibility and inflammatory response phenotypes. These findings point to the complex link between skin tumor susceptibility and inflammatory response in mice.
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http://dx.doi.org/10.1016/j.canlet.2010.02.013DOI Listing
September 2010

Gene expression profiles of bone marrow cells from mice phenotype-selected for maximal or minimal acute inflammations: searching for genes in acute inflammation modifier loci.

Immunology 2009 Sep 18;128(1 Suppl):e562-71. Epub 2008 Dec 18.

Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.

Two mouse lines were phenotype-selected for maximum (AIRmax) or minimum (AIRmin) acute inflammation responses to polyacrylamide bead (Biogel) injection. These lines differ in terms of bone marrow granulopoiesis, neutrophil resistance to apoptosis, and inflammatory cytokine production during acute inflammation responses. We compared gene expression profiles in bone marrow cells (BMC) of AIRmax and AIRmin mice during acute inflammatory reactions. The BMC from femurs were recovered 24 hr after subcutaneous injections of Biogel. Global gene expression analysis was performed on CodeLink Bioarrays (36K genes) using RNA pools of BMC from both control and treated AIRmax and AIRmin mice. Differentially expressed genes were statistically established and the over-represented gene ontology biological process categories were identified. Upregulations of about 136 and 198 genes were observed in the BMC of Biogel-treated AIRmax and AIRmin mice, respectively, but 740 genes were found to be downregulated in AIRmin mice compared with 94 genes in AIRmax mice. The over-represented biological themes of the differently expressed genes among AIRmax and AIRmin mice represent inflammatory response, signal transduction, cell proliferation and immune cell chemotaxis. We were able to demonstrate a broad downmodulation of gene transcripts in BMC from AIRmin mice during acute inflammation, and significant differentially expressed genes colocalized with previously mapped regions for inflammation-related phenotypes in chromosomes 1, 3, 6 and 11.
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http://dx.doi.org/10.1111/j.1365-2567.2008.03032.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753958PMC
September 2009

Aryl hydrocarbon receptor polymorphism modulates DMBA-induced inflammation and carcinogenesis in phenotypically selected mice.

Int J Cancer 2009 Mar;124(6):1478-82

Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.

We tested the role of aryl hydrocarbon receptor (Ahr) gene polymorphism in the inflammatory response and in skin and lung tumorigenesis in 2 lines of mice phenotypically selected for maximum or minimum acute inflammatory reaction (AIRmax and AIRmin, respectively). Following 7,12-dimethylbenz[a]anthracene (DMBA) treatment, AIRmin but not AIRmax mice showed early skin reactions and eventually developed malignant skin tumors and lung adenocarcinomas. In skin tissue, transcript levels of IL1beta, Tnf, Il6, Tgfbeta1 and Cyp1b1 genes were upregulated in AIRmin but not AIRmax mice, consistent with the inflammatory responses to the carcinogen. These findings appeared to be related to the homozygosity status of the Ahr functional A375V polymorphism, which influences the binding capability of the receptor for DMBA: the 375A allele, encoding the high-affinity ligand-binding receptor (Ahr(b1)), segregated in AIRmin mice, whereas AIRmax mice carried the 375V, corresponding to the low-affinity binding receptor (Ahr(d)), to DMBA. The differential segregation of Ahr functional Ahr(d)versus Ahr(b1) alleles in AIRmax and AIRmin suggests a role for the Ahr gene in the control of inflammatory responsiveness and tumor development of these mouse lines.
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http://dx.doi.org/10.1002/ijc.24066DOI Listing
March 2009

Bothrops jararaca venom (BjV) induces differential leukocyte accumulation in mice genetically selected for acute inflammatory reaction: the role of host genetic background on expression of adhesion molecules and release of endogenous mediators.

Toxicon 2008 Oct 6;52(5):619-27. Epub 2008 Aug 6.

Laboratório de Imunogenética, Instituto Butantan, Av. Vital Brasil 1500 - cep 05503-900, São Paulo, SP, Brazil.

The dynamics of the local inflammatory events induced by Bothrops jararaca venom (BjV) inoculation in footpad of mice genetically selected for maximal (AIRmax) and minimal (AIRmin) acute inflammatory reactivity (AIR) was investigated. The BjV injection induced a marked inflammatory cell infiltrate with predominance of neutrophils, with increased blood cell numbers before its accumulation, suggesting a stimulatory action of BjV on mechanisms of cell mobilization from bone marrow. The process of cell migration is regulated by different cell-adhesion molecules (CAM). Our results showed that neutrophil cells from both lines had the same pattern of response concerning CAMs expression, presenting the involvement of l-selectin, Mac-1 and PECAM-1 adhesion molecules in BjV-induced neutrophil accumulation. The effect of BjV on the release of pro-inflammatory cytokines and chemokines related with cellular migration was also studied and IL-1beta, IL-6, TNF-alpha and MIP-2 levels could be detected after venom injection. The AIRmax mice were shown to be more responsive than AIRmin with respect to leukocyte influx, expression of MIP-2 and release of IL-1beta and IL-6. These results demonstrate the importance of host genetic background in the local response and the involvement of alleles accumulated in AIRmax mice in the inflammatory events induced by BjV.
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http://dx.doi.org/10.1016/j.toxicon.2008.07.012DOI Listing
October 2008

Slc11a1 (Nramp1) alleles interact with acute inflammation loci to modulate wound-healing traits in mice.

Mamm Genome 2007 Apr 8;18(4):263-9. Epub 2007 May 8.

Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil.

Lines of mice were obtained by selective breeding for maximum (AIRmax) or minimum (AIRmin) acute inflammation. They present distinct neutrophil influx and show frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) alleles. This gene is involved in ion transport at the endosomes within macrophages and neutrophils, interfering in their activation. Homozygous AIRmax and AIRmin sublines for the Slc11a1 gene were produced to examine the interaction of this gene with the acute inflammatory loci. The present work investigated wound-healing traits in AIRmax and AIRmin mice, in F(1) and F(2) intercrosses, and in Slc11a1 sublines. Two-millimeter ear punches were made in the mice and hole closure was measured during 40 days. AIRmax mice demonstrated significant tissue repair while AIRmin mice did not. Significant differences between the responses of male and female mice were also observed. Wound-healing traits demonstrated a correlation with neutrophil influx in F(2) populations. AIRmax( SS )showed higher ear-wound closure than AIRmax( RR ) mice, suggesting that the Slc11a1 S allele favored ear tissue repair. QTL analysis has detected two inflammatory loci modulating ear wound healing on chromosomes 1 and 14. These results suggest the involvement of the acute inflammation modifier QTL in the wound-healing phenotype.
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http://dx.doi.org/10.1007/s00335-007-9012-xDOI Listing
April 2007

Local inflammatory reaction induced by Bothrops jararaca venom differs in mice selected for acute inflammatory response.

Toxicon 2002 Nov;40(11):1571-9

Laboratório de Imunogenética, Instituto Butantan, Av Vital Brasil 1500-cep 05503-900 São Paulo, SP, Brazil.

Bothrops jararaca venom (BjV) causes severe systemic and local reactions, characterized by an acute inflammatory reaction with accumulation of leukocytes and release of endogenous mediators. The systemic and local effects of BjV were compared in lines of mice genetically selected for maximal (AIR(max)) or minimal (AIR(min)) acute inflammatory reactivity (AIR). The systemic reaction was evaluated by LD(50) and the local reaction by edema formation, cellular influx, release of PGE(2), NO and H(2)O(2) and the production of the pro-inflammatory cytokines IL-6, Tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Both mouse lines were equally susceptible to the lethal effects of the venom showing similar LD(50) but differed significantly in terms of the local inflammatory reaction. Footpad edema and leukocyte influx in the peritoneum after BjV inoculation was higher in AIR(max) compared to AIR(min), BALB/c or outbred Swiss mice. Coincidently, higher levels of the soluble mediators PGE(2), IFN-gamma and TNF-alpha were detected in the inflammatory exudate induced by BjV in AIR(max) mice. Cytokines levels were correlated to in vitro NO and H(2)O(2) production. The results demonstrate that the genetic factors selected in AIR(max) and AIR(min) lines of mice interfere in the control of the acute local reaction triggered by BjV venom.
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http://dx.doi.org/10.1016/s0041-0101(02)00174-5DOI Listing
November 2002