RESUMO
BACKGROUND: There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression. OBJECTIVES: The aim of this study was to evaluate whether 3 months of monotherapy with chloroquine influences the mRNA skin expression of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in nonirradiated and locally ultraviolet B (UVB) irradiated nondiseased skin of patients with systemic lupus erythematosus (SLE). PATIENTS/METHODS: Skin biopsies were collected from 14 patients with SLE 24 h after irradiation at one site and from an adjacent unirradiated site, before and after 3 months of chloroquine treatment. Messenger RNA levels for IL-1beta, IL-6 and TNF-alpha were determined by relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: There were no significant differences in the levels of mRNA cytokine expressions in the unirradiated sites before and after 3 months of chloroquine administration. In the irradiated sites, the expression of all three cytokine mRNA levels was significantly higher than in the unirradiated group, approximately 24 h after irradiation, before chloroquine treatment. Significantly lower expression of IL-1beta, IL-6 and TNF-alpha mRNAs was noted in irradiated skin samples after 3 months of chloroquine treatment. CONCLUSIONS: These results demonstrate the local inhibitory effects of chloroquine on UVB-induced upregulation in the mRNA expression of proinflammatory cytokines in irradiated skin of SLE patients, and provide further insight into the apparent immunomodulatory, anti-inflammatory and photoprotective properties of chloroquine.
Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Citocinas/metabolismo , Lúpus Eritematoso Sistêmico/tratamento farmacológico , RNA Mensageiro/análise , Pele/efeitos da radiação , Adulto , Citocinas/genética , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Raios Ultravioleta , Adulto JovemRESUMO
We analysed the distribution of genotypes of two polymorphisms in the urokinase-type plasminogen activator (uPA) gene: C-->T substitution in exon 6 and T-->C substitution in intron 7 in 52 subjects with colorectal cancer. Genotypes were determined in tumour tissue and distant mucosa samples by allele-specific polymerase chain reaction. The antigen levels of uPA in cancer tissue were higher than in distant mucosa as measured by enzyme-linked immunosorbent assay. The level of uPA antigens in cancer samples with the C/C genotype of C-->T polymorphism in exon 6 was higher than in samples with C/T and T/T genotypes. No differences in the level of uPA antigens between the alleles of the intron 7 T-->C polymorphism were found. As uPA can be involved in cancer invasion and metastasis, C/C genotype in exon 6 of uPA gene can be further considered as being related to colorectal cancer progression.
Assuntos
Neoplasias Colorretais/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/imunologia , Idoso , Antígenos/análise , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Urokinase plasminogen activation system can play an important role in the appearance and progression of many cancers. Urokinase-type plasminogen activator (uPA) is implicated in the control of cell adhesion and invasion, and is regarded as a strong prognostic marker in colorectal cancer. A C-->T substitution (the C/T polymorphism) in the nucleotide sequence encoding the kringle structure of uPA results in an alteration from proline to leucine at position 121. This substitution may be directly or indirectly involved in the decreased affinity for uPA substrates. In the present work the distribution of genotypes and frequencies of alleles of the C/T polymorphism were investigated. Tumour tissues and distal mucosa samples were obtained from 40 patients with colorectal cancer. Blood samples from sex and age matched healthy individuals served as control. The C/T polymorphism was determined by PCR amplification using the allele specific primers. No differences between genotypes of the C/T polymorphism in cancer tissue and distant mucosa of each patient were found. The distributions of the genotypes in both patients and control differed significantly (p < 0.05) from that predicted by the Hardy-Weinberg distribution. A distinct preference of heterozygotes (70% - patients, 65% - controls) was observed in both patients and controls. Additionally, there were no differences in the frequencies of the C and T alleles in both groups. The C/T polymorphism of the uPA gene may not be linked with colorectal cancer.
