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

Abstract

Summary 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.

Genetic Control of IL-1β Production and Inflammatory Response by the Mouse Irm1 Locus

“…The different response of BM from AIRmax and AIRmin mice treated with Biogel suggests that the genetic trait of acute inflammatory response may be mediated by differences in the transcriptome profile of BM (3).…”

Genetic Predisposition to Hepatocarcinogenesis in Inbred and Outbred Mouse Lines Selected for High or Low Inflammatory Response

“…H2Ea: mice bearing the H2b haplotype do not express I-E MHC class II molecules, due to deletion of the promoter region of the Ea gene. We verified before that the majority of AIRmax mice bear the H2b haplotype which might underlie the absence of H2Ea expression in the liver as well as in all tissues tested so far [11, 12]. AIRmax mice are susceptible to autoimmune diseases such as pristane-induced arthritis, and the E-alpha chain was described as protective to the development of systemic lupus erythematosus [48].…”

“…AIRmax are more susceptible than AIRmin to colon carcinogenesis [7] while AIRmin are more susceptible to skin, lung, and kidney carcinogenesis [8–10]. The two strains have distinct gene expression profiles in the bone marrow and in the normal lung [11, 12] which correlated with their differential inflammation capacity and tumor susceptibility, respectively.…”

Mielotoxicidade por 7,12-dimetilbenzantraceno e sua repercurssão na resposta imunológica dos camundongos AIRmax e AIRmin.

“…Baseando-se nesses critérios, avaliamos os efeitos genotóxicos e citotóxicos produzidos pelo DMBA no período de 24 horas após tratamento in vivo e in vitro. Na análise ex vivo verificamos que após 2 horas do tratamento com DMBA houve um efeito genotóxico em ambas as linhagens AIRmax e AIRmin, quando comparados com os animais controles que Em camundongos isogênicos e geneticamente selecionados o tratamento epicutâneo com DMBA induziu, na medula óssea, um aumento da expressão de alguns genes relacionados com a sinalização para apoptose e para reparo de DNA por qPCR (EMBER et al, 1998;CARNEIRO, P. et al, 2009).…”