ABSTRACT
We aimed to investigate the association of CD14 -260C/T (rs2569190) polymorphism and Chagas cardiomyopathy and the functional characteristics of CD14+ and CD14- monocytes upon infection with Trypanosoma cruzi. We observed an association between the T- genotype (absence of allele -260T) related to low CD14 expression and the dilated cardiomyopathy type of Chagas disease. Furthermore, we observed that CD14- monocytes showed a more activated profile upon in vitro infection with T. cruzi than CD14+ monocytes. Our findings suggest that T- genotype is associated with susceptibility to develop Chagas dilated cardiomyopathy, likely linked to the T. cruzi-induced inflammatory profile of CD14- monocytes.
Subject(s)
Humans , Cardiomyopathy, Dilated/genetics , Chagas Cardiomyopathy/genetics , Lipopolysaccharide Receptors/genetics , Trypanosoma cruzi , Chagas Disease , Ventricular Dysfunction, Left , Genotype , Heart FailureABSTRACT
CONTEXT: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes. AIMS: The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India. SETTINGS AND DESIGN: Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg’s equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively). CONCLUSION: COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.
Subject(s)
Aged , Lipopolysaccharide Receptors/genetics , Asthma/epidemiology , Bhopal Accidental Release , Chronic Disease , Female , Humans , Isocyanates/adverse effects , Lung Diseases/chemically induced , Lung Diseases/epidemiology , Lung Diseases/etiology , Lung Diseases/genetics , Male , Middle Aged , Polymorphism, Genetic , Population Groups/epidemiology , Population Groups/geneticsABSTRACT
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.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Alleles , Lipopolysaccharide Receptors/genetics , Asian People/genetics , Colitis, Ulcerative/genetics , Crohn Disease/genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Inflammatory Bowel Diseases/genetics , 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/geneticsABSTRACT
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.
Subject(s)
Female , Humans , Middle Aged , Young Adult , Lipopolysaccharide Receptors/genetics , Colitis, Ulcerative/diagnosis , Colonoscopy , Crohn Disease/diagnosis , Genetic Predisposition to Disease , Mesalamine/therapeutic use , Mothers , Polymorphism, Restriction Fragment Length , Tomography, X-RayABSTRACT
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.
Subject(s)
Female , Humans , Middle Aged , Young Adult , Lipopolysaccharide Receptors/genetics , Colitis, Ulcerative/diagnosis , Colonoscopy , Crohn Disease/diagnosis , Genetic Predisposition to Disease , Mesalamine/therapeutic use , Mothers , Polymorphism, Restriction Fragment Length , Tomography, X-RayABSTRACT
CD14 is a leukocyte surface molecule expressed on monocytes but not on lymphocytes. Recently, CD14 molecule was demonstrated to function as a receptor for endotoxin. CD14 specific monoclonal antibody (MAb), therefore, can be used to identify monocytes and study the host defense mechanism to bacterial endotoxin. To produce MAb against CD14 protein, in this study cDNA encoding CD14 protein and COS cell expression systems were used to prepare CD14 expressing COS cells. The CD14 transfectants were then used as antigen for mouse immunization. The spleen cells of the immunized mouse were then fused with myeloma cells by conventional hybridoma technique. By using this strategy, 5 hybridroma clones secreting antibody specific for CD14 molecule were generated within one fusion. The generated CD14 MAbs were strongly positive with monocytes, weakly positive with neutrophils but negative with lymphocytes. In addition, the generated CD14 MAb blocked the binding of lipopolysaccharide (LPS) to the CD14 molecules. These CD14 MAbs could be used to enumerate peripheral blood monocytes as well as using referent CD14 MAb. We, therefore, introduce an alternative method for preparation of antigen for production of monoclonal antibody. This type of antigen is a very effective antigen for the production of monoclonal antibodies against cell surface molecules.