Slc11a1 (Nramp-1) gene modulates immune-inflammation genes in macrophages during pristane-induced arthritis in mice

Corrêa, Mara Adriana; Canhamero, Tatiane; Borrego, Andrea; Katz, Iana Suly Santos; Jensen, José Ricardo; Guerra, José Luiz; Cabrera, Wafa Hanna Koury; Starobinas, Nancy; Fernandes, Jussara Gonçalves; Ribeiro, Orlando; Ibañez, Olga M.; Franco, Marcelo De

doi:10.1007/s00011-017-1077-8

Cited by 20 publications

(20 citation statements)

References 74 publications

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“…Seven genes were hypermethylated and 4 genes were hypomethylated. The hypermethylated genes have roles in asthma (VGLL4, AGR2) ( 24 , 28 ), neurologic development (AGAP1, OTX2) ( 29 , 30 ), and immune regulation (SCAMP5, SLC11A1) ( 31 , 32 ). The hypomethylated genes have roles in immune regulation (PPP4C) ( 27 ), transcription regulation (MIER2) ( 26 ), and inflammation (ABCC8) ( 33 ).…”

Section: Resultsmentioning

confidence: 99%

DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis

et al. 2020

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Background: Histological chorioamnionitis (HCA) is an infection/inflammation of fetal membranes and complicates 5.2-28.5% of all live births. Exposure to HCA can have long-term consequences including abnormal neurodevelopment and an increased risk for allergic disorders and asthma later in childhood. HCA may incite epigenetic changes, which have the potential to modulate both the immune and neurological systems as well as increase the risk of related disorders later in life. However, there is limited data on the impact of HCA on epigenetics, in particular DNA methylation, and changes to immune and neurological systems in full-term human neonates. Objective: To determine differential DNA methylation in cord blood mononuclear leukocytes from neonates exposed to HCA. Methods: Cord blood was collected from 10 term neonates (5 with HCA and 5 controls without HCA) and mononuclear leukocytes were isolated. Genome-wide DNA methylation screening was performed on Genomic DNA extracted from mononuclear leukocytes. Results: Mononuclear leukocytes from cord blood of HCA-exposed neonates showed differential DNA methylation of 68 probe sets compared to the control group (44 hypermethylated, 24 hypomethylated) with a p ≤ 0.0001. Several genes involved in immune modulation and nervous system development were found to be differentially methylated. Important canonical pathways as revealed by Ingenuity Pathway Analysis (IPA) were CREB Signaling in Neurons, FcγRIIB Signaling in B Lymphocytes, Cell Cycle:

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Section: Resultsmentioning

confidence: 99%

DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis

et al. 2020

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“…Our results with AIRmaxSS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H 2 O 2 , NO, IL-1b, IL-6, TNF-a, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development [ 16 ]. Pristane, hexadecane, squalene, and mineral oil also induce arthritis in Lewis and Dark Agouti rats.…”

Section: Discussionmentioning

confidence: 99%

“…In our linkage studies using AIRmax x AIRmin intercrosses, we mapped quantitative trait loci (QTL) for PIA susceptibility on chromosomes 5 and 8 that overlap QTL for experimental arthritis and other autoimmune diseases [ 2 ]. Gene expression profiling of paws from arthritic and nonarthritic AIRmax and AIRmin mice showed that among several differentially regulated genes, IL-1beta and CXC chemokines had higher expression in PIA-susceptible AIRmax mice, as well as in macrophages [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Mice Selected for Acute Inflammation Present Altered Immune Response during Pristane-Induced Arthritis Progression

Corrêa

Borrego

Jensen

et al. 2018

BioMed Research International

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Mouse lines selected for maximal (AIRmax) or minimal acute inflammatory reaction (AIRmin) were used to characterize the immune response and the influence of genetic background during pristane-induced arthritis (PIA). Susceptible AIRmax mice demonstrated exacerbated cellular profiles during PIA, with intense infiltration of lymphocytes, as well as monocytes/macrophages and neutrophils, producing higher levels of IL-1β, IFN-γ, TNF-α, IL-10, total IgG3, and chemokines. Resistant AIRmin mice controlled cell activation more efficiently than the AIRmax during arthritis progression. The weight alterations of the spleen and thymus in the course of PIA were observed. Our data suggest that selected AIRmax cellular and genetic immune mechanisms contribute to cartilage damage and arthritis severity, evidencing many targets for therapeutic actions.

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“…The unbalanced expression of the genes that promote osteoclastogenesis and inhibit osteoblast differentiation may represent a mechanism stimulating bone erosion and increasing disease severity in AIRmax animals. Histological analyses of the paws of the AIRmaxSS subline did, in fact, show bone loss in addition to the destruction of cartilage [42].…”

Section: Discussionmentioning

confidence: 99%

miRNA Expression and Interaction with Genes Involved in Susceptibility to Pristane-Induced Arthritis

Fernandes

Borrego

Jensen

et al. 2018

Journal of Immunology Research

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Pristane-induced arthritis (PIA) in mice is an experimental model that resembles human rheumatoid arthritis, a chronic autoimmune disease that affects joints and is characterized by synovial inflammation and articular cartilage and bone destruction. AIRmax and AIRmin mouse lines differ in their susceptibility to PIA, and linkage analysis in this model mapped arthritis severity QTLs in chromosomes 5 and 8. miRNAs are a class of small RNA molecules that have been extensively studied in the development of arthritis. We analyzed miRNA and gene expression profiles in peritoneal cells of AIRmax and AIRmin lines, in order to evaluate the genetic architecture in this model. Susceptible AIRmax mice showed higher gene (2025 vs 1043) and miRNA (240 vs 59) modulation than resistant AIRmin mice at the onset of disease symptoms. miR-132-3p/212-3p, miR-106-5p, miR-27b-3p, and miR-25-3p were among the miRNAs with the highest expression in susceptible animals, showing a negative correlation with the expression of predicted target genes (Il10, Cd69, and Sp1r1). Our study showed that global gene and miRNA expression profiles in peritoneal cells of susceptible AIRmax and resistant AIRmin lines during pristane-induced arthritis are distinct, evidencing interesting targets for further validation.

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Slc11a1 (Nramp-1) gene modulates immune-inflammation genes in macrophages during pristane-induced arthritis in mice

Abstract: Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.

Cited by 20 publications

References 74 publications

DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis

DNA Methylation Profile in Human Cord Blood Mononuclear Leukocytes From Term Neonates: Effects of Histological Chorioamnionitis

Mice Selected for Acute Inflammation Present Altered Immune Response during Pristane-Induced Arthritis Progression

miRNA Expression and Interaction with Genes Involved in Susceptibility to Pristane-Induced Arthritis

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