RESUMO
Toll-like receptors (TLRs), the triggers of the innate and adaptive immune responses, are involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Several studies have investigated the effects of genetic polymorphisms in TLR4 and TLR2, but they have yielded limited results. We investigated whether non-missense genetic polymorphisms in the regulatory regions of TLR4 and TLR2 were related to T2DM in a southern Chinese population. Single nucleotide polymorphisms (SNPs) in TLR4 (rs1927911, rs11536889, rs1927907, rs1927906, rs1927914, rs7873784, and rs2149356) and TLR2 (rs1898830, rs3804099, rs4696480, and rs3804100) were genotyped in 552 T2DM and 552 unrelated age- and gender-matched controls by SNaPShot Multiplex assay. Genotypes GG (OR = 0.09, 95%CI = 0.01- 0.83, P = 0.03) and CG (OR = 0.08, 95%CI = 0.01-0.74, P = 0.03) of the 3'-untranslated region (UTR) SNP rs7873784 in TLR4, and genotype AG (OR = 0.67, 95%CI = 0.46-0.97, P = 0.04) and allele G (OR = 0.88, 95%CI = 0.79-0.97, P = 0.01) of the intron SNP rs1898830 in TLR2 were identified as protective against the development of T2DM in southern Chinese people. In contrast, a meta-analysis of rs1927911 and rs1927914 showed no association. Haplotypes AGTT (OR = 0.34, 95%CI = 0.15-0.77, P = 0.01) and AATT (OR = 1.20, 95%CI = 1.01- 1.44, P = 0.05) in TLR2 were significantly associated with susceptibility to T2DM. Our results suggest that the effects of non-missense polymorphisms located in the regulatory regions of TLR4 and TLR2 should not be neglected in T2DM association analysis.
Assuntos
Diabetes Mellitus Tipo 2/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Idoso , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We investigated the roles of CD3McAb and rhIL-2 activated bone marrow in the killing and purging of leukemia cells. Cytotoxicity of activated bone marrow was detected with MTT assay. CFU-GM level in activated bone marrow and the destruction of leukemia cells were measured using the semi-solid cell culture. Immune activation markers in activated bone marrow were detected by indirect immunofluorescence assay. Bone marrow activated by CD3McAb and rhIL-2 displayed significantly upregulated the killing and purging abilities on the leukemia cell line K562 and HL-60. Such effects were superior to that of bone marrow activated by rhIL-2 or CD3McAb alone (P < 0.05, P < 0.01). Activation by rhIL-2 and (or) CD3McAb exerted no obvious influence on CFU-GM level in bone marrow. Compared with bone marrow activated by rhIL-2 or CD3McAb alone, the synergistic effect of both CD3McAb+ and hIL-2 caused significant increase of CD3(+), CD8(+), CD19(+), CD25(+), CD38(+), and CD56(+) levels. Our study indicates that CD3McAb enhanced the killing and purging effects of rhIL-2 activated bone marrow on leukemia cells.