Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder. Inappropriate and exaggerated immune response for the luminal antigen is known as a main pathogenesis. Genetic, infectious, and environmental factors are responsible for unbalanced immune response, but the definite pathogenesis is still unclear. Genetic factor is the most important role of all. That is based on high concordance rate of identical twins and family history. The incident rate and prevalence of IBD for the Asian population is relatively lower than Western population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and Japanese population suggests the difference in genetic background between Asian and Western population. In Korea, the case of familial aggregation of IBD is pretty rare. We report a case of the daughter with ulcerative colitis and her mother with Crohn's disease who have a -159C/T promoter polymorphism of CD14 gene for IBD.
Antigens, CD14/genetics ; Colitis, Ulcerative/*diagnosis/drug therapy/genetics ; Colonoscopy ; Crohn Disease/*diagnosis/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Mesalamine/therapeutic use ; Middle Aged ; Mothers ; Polymorphism, Restriction Fragment Length ; Tomography, X-Ray ; Young Adult

Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder. Inappropriate and exaggerated immune response for the luminal antigen is known as a main pathogenesis. Genetic, infectious, and environmental factors are responsible for unbalanced immune response, but the definite pathogenesis is still unclear. Genetic factor is the most important role of all. That is based on high concordance rate of identical twins and family history. The incident rate and prevalence of IBD for the Asian population is relatively lower than Western population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and Japanese population suggests the difference in genetic background between Asian and Western population. In Korea, the case of familial aggregation of IBD is pretty rare. We report a case of the daughter with ulcerative colitis and her mother with Crohn's disease who have a -159C/T promoter polymorphism of CD14 gene for IBD.
Antigens, CD14/genetics ; Colitis, Ulcerative/*diagnosis/drug therapy/genetics ; Colonoscopy ; Crohn Disease/*diagnosis/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Mesalamine/therapeutic use ; Middle Aged ; Mothers ; Polymorphism, Restriction Fragment Length ; Tomography, X-Ray ; Young Adult

The innate immune response in patients who develop inflammatory bowel disease (IBD) may be abnormal. However, the exact role of Toll-like receptors (TLRs) / CD14 gene in the pathogenesis of IBD has not been fully elucidated. We aimed to investigate the association between polymorphisms of TLR1, 2, 4, 6, and CD14 gene and susceptibility to IBD in Korean population. A total 144 patients of IBD (99 patients with ulcerative colitis, 45 patients with Crohn's disease) and 178 healthy controls were enrolled. Using a PCR-RFLP, we evaluated mutations of TLR1 (Arg80Thr), TLR2 (Arg753Gln and Arg677Trp), TLR4 (Asp299Gly and Thr399Ile), TLR6 (Ser249Pro) genes and the -159 C/T promoter polymorphism of CD14 gene. No TLR polymorphisms were detected in Korean subjects. T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls. In subgroup analysis, T allelic frequency was higher in pancolitis phenotype of ulcerative colitis. In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohn's disease.
Adult ; Aged ; Alleles ; Antigens, CD14/*genetics ; Asian Continental Ancestry Group/*genetics ; Colitis, Ulcerative/genetics ; Crohn Disease/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Inflammatory Bowel Diseases/*genetics ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Republic of Korea ; Toll-Like Receptor 1/genetics ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 6/genetics ; Toll-Like Receptors/*genetics

To characterize the TGF-beta1 response of monocytic leukemia cells, we analyzed the effects of TGF-beta1 on cell proliferation, differentiation, and apoptosis of human monoblastic U937 cells. Treatment of cells with TGF-beta1 in the absence of growth factors significantly enhanced cell viability. Flow cytometric analysis of DNA content and CD14 expression revealed that TGF-beta1 does not affect cell proliferation and differentiation. Consistent with these results was the finding that no transcriptional induction of Cdk inhibitors such as p21Waf1, p15Ink4b, and p27Kip1 was detected following TGF-beta1 treatment. Interestingly, however, pretreatment of TGF-beta1 significantly inhibited Fas-, DNA damage-, and growth factor deprivation-induced apoptosis. This antiapoptotic effect was totally abrogated by anti-TGF-beta1 antibody. Quantitative RT-PCR analysis demonstrated a dose- and time-dependent transcriptional up-regulation of Bcl-X(L), suggesting its implication in the TGF-1-mediated antiapoptotic pathway. We also observed elevated expression of c-Fos and PTEN/MMAC1. But, no detectable change was recognized in expression of c-Jun, Fas, Fadd, Fap-1, Bcl-2, and Bax. Taken together, our study shows that TGF-beta1 enhancement of cellular viability is associated with its antiapoptotic effect, which may result from the transcriptional up-regulation of Bcl-X(L).
Antigens, CD14/metabolism ; Antigens, CD95/metabolism ; Apoptosis/drug effects* ; Cell Cycle/drug effects ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cell Survival/drug effects ; DNA/analysis ; DNA Damage ; Gene Expression Regulation, Neoplastic/genetics* ; Genes, Suppressor, Tumor/genetics ; Human ; Leukemia, Myeloid/genetics ; Neoplasm Proteins/metabolism ; Phosphoric Monoester Hydrolases/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; RNA, Messenger/metabolism ; Receptors, Antigen, T-Cell/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Transforming Growth Factor beta/pharmacology* ; U937 Cells ; Up-Regulation (Physiology)