Pristane-induced arthritis in mice selected for maximal or minimal acute inflammatory reaction

Vigar, Nicole D.; Cabrera, Wafa Hanna Koury; Araujo, Luiza M.; Ribeiro, Orlando; Ogata, Terezinha Regina Prúpere; Siqueira, Maria; Ibañez, Olga M.; Franco, Marcelo De

doi:10.1002/1521-4141(200002)30:2<431::aid-immu431>3.0.co;2-4

Cited by 53 publications

(40 citation statements)

References 25 publications

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“…However, for other inflammatory stimuli such as Biogel induced subcutaneous inflammation 10 , in arthritic joints induced by pristane treatment, 11 or in colon after Dextran induced acute colitis, 12 the production of inflammatory cytokines was significantly higher in AIRmax in comparison with AIRmin. Cyp1b1 is transcriptionally regulated by Ahr and is primarily involved in metabolism of foreign chemicals 13 .…”

Section: Resultsmentioning

confidence: 95%

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

Souza

Cabrera

Galvan

et al. 2008

Intl Journal of Cancer

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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,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 IL1b, Tnf, Il6, Tgfb1 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 Key words: aryl hydrocarbon receptor; DMBA; inflammation; carcinogenesis; selected mice Two nonisogenic mouse lines derived by bidirectional selection based on the intensity of local acute inflammatory reactions (AIR) to polyacrylamide beads (Biogel) 1 have shown striking differences in resistance/susceptibility to chemical-induced carcinogenesis. Mice with the maximum acute inflammatory reaction (AIRmax) are significantly more resistant than minimum responders (AIRmin) to two-stage skin tumorigenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) followed by repeated doses of the promoter agent 12-O-tetradecanoyl-phorbol-13-acetate (TPA), 2 and also to lung carcinogenesis induced by urethane, 3 suggesting that a subset of loci affecting the inflammatory response also act as cancer modifier loci.DMBA and other polycyclic aromatic hydrocarbon compounds (PAHs) exert carcinogenic effects following metabolic activation mediated by the intracellular aryl hydrocarbon receptor (Ahr), a ligand-activated transcriptional factor regulating the induction of mono-oxygenase enzymes that convert the parent DMBA compound to a diol epoxide, the actual carcinogenic moiety. 4 Ahr gene presents functional polymorphism, which accounts for differences in responses of mouse strains to PAHs. 5 We investigated DMBA-induced skin contact reactions and skin and lung tumor development in AIR mice with respect to their allele status of the Ahr gene. Our results implicate Ahr in tumor susceptibility and in inflammatory response control in AIRmax and AIRmin mice. Material and methods Mice and tumor inductionAIRmax and AIRmin mice from the 38th generation of selective breedings were produced at Laboratory of Immunogenetics of Butantan Institute (São Paulo, Brazil). All experimental procedures were approved by the Animal Experimentation Ethics Committee of the Institute. Doses of 50 lg DMBA (Sigma, St. Louis, MO) in 0.1 ml acetone were applied to the shaved dorsal skin of mice during 5 consecutive days. Skin tumors were scored twice a week in groups of 15 AIRmax and 15 AIRmi...

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Section: Resultsmentioning

confidence: 95%

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

Souza

Cabrera

Galvan

et al. 2008

Intl Journal of Cancer

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“…AIRmax mice are extremely susceptible to PIA, whereas AIRmin mice are resistant. 14 The incidence and severity of PIA in AIRmax mice was similar to that of inbred DBA/1 mice, 15 but more intense than in BALB/c 6 and CBA Igh b 10 mice. In contrast to the immune response profile observed in inbred mice, high IgG1 anti-hsp65 levels were observed in susceptible AIRmax mice, whereas IgG2a was the predominant isotype in the resistant AIRmin mice.…”

Section: Introductionmentioning

confidence: 77%

“…CBA 7 inbred mice bearing the R allele are susceptible to this disease, whereas arthritis incidence in BALB/c 6 and DBA/1 15 mice bearing the S allele is about 15 and 80%, respectively. Overall, AIRmax animals had the highest PIA incidence, 14 suggesting the involvement of other AIR QTL in arthritis progression.…”

Section: Discussionmentioning

confidence: 95%

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Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

et al. 2006

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Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax RR , AIRmax SS , AIRmin RR and AIRmin SS lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax RR mice reached 29%, whereas PIA incidence in AIRmax SS mice was 70% by day 180. AIRmin RR mice were resistant, whereas 13.3% of AIRmin SS mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1 SS mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.

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“…Este modelo animal também tem demonstrado ser muito adequado para o estudo dos mecanismos de resposta inflamatória aguda e suas interações com a resposta imune específica em doenças autoimunes (VIGAR et al, 2000;PETERS et al, 2007), tumorais (BIOZZI et al, 1998;MARIA et al, 2003) e infecciosas VORRARO, 2001). Além de apresentarem um perfil distinto de resposta na cicatrização e reparo tecidual (DE FRANCO et al, 2007 análise da sequência da proteína do gene Nramp1 entre as duas formas alélicas (R e S) revelou que uma única mutação, ou seja, uma substituição não conservada do aminoáocido glicina por ácido aspártico na posição 169 do códon, dentro do quarto domínio transmembrânico da proteína, resulta na sua completa falta de função em camundongos susceptíveis (VIDAL et al, 1996).…”

Section: Seleção De Genética Bidirecional De Linhagens De Camundongosunclassified

Estudo do envolvimento dos loci reguladores da reação inflamatória aguda na determinação da sensibilidade ou resistência ao choque endotóxico induzido por lipopolissacarídeo.

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Pristane-induced arthritis in mice selected for maximal or minimal acute inflammatory reaction

Cited by 53 publications

References 25 publications

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

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

Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

Estudo do envolvimento dos loci reguladores da reação inflamatória aguda na determinação da sensibilidade ou resistência ao choque endotóxico induzido por lipopolissacarídeo.

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