Polymorphisms in the surfactant protein a gene are associated with the susceptibility to recurrent urinary tract infection in chinese women.
ABSTRACT Some risk factors for susceptibility to recurrent urinary tract infection (r-UTI) are well known, but the genetic role in acquiring the disease is poorly understood. Surfactant protein A and D (SP-A and SP-D) play an important role in modulation of lung inflammatory processes. The SP-A1 and SP-A2 genes encoding SP-A and the SP-D gene are highly polymorphic, and some of polymorphisms are associated with several infective diseases, including pyelonephritis. In the present study, we investigated whether some of these polymorphisms are associated with the risk of r-UTI in Chinese population. Genomic DNA was extracted from blood samples of 32 female patients with r-UTI and 30 age-matched, unrelated healthy female subjects. Genotyping of gene polymorphisms was analyzed by PCR. Among 11 single nucleotide polymorphisms (SNPs) (five of SP-A1, four of SP-A2 and two of SP-D) observed in the enrolled subjects, Ala19Val of SP-A1 and Lys223Gln of SP-A2 were associated with susceptibility to r-UTI. The frequencies of 19Ala allele of SP-A1 gene (p = 0.038) and 223Gln allele of SP-A2 gene (p = 0.012) in the patients were significantly higher than those in healthy subjects. The serum SP-A and SP-D levels were increased and the urine SP-A and SP-D levels were decreased in r-UTI patients compared with control subjects (p < 0.05). r-UTI patients with 19Ala/Ala or 223Gln/Gln genotype were associated with high serum and low urine SP-A levels (p < 0.01). Therefore, the 19Ala allele of SP-A1 gene and the 223Gln allele of SP-A2 gene are risk factors for r-UTI.
SourceAvailable from: Satoshi Takahashi[Show abstract] [Hide abstract]
ABSTRACT: The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a lectin located at bacterial pili, and their interaction initiates UPEC infection. Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in various tissues besides the lung. However, the functions of SP-D in the non-pulmonary tissues are poorly understood. The purposes of this study were to investigate the possible function of SP-D expressed in the bladder urothelium and the mechanisms by which SP-D functions. SP-D was expressed in human bladder mucosa and its mRNA was increased in the bladder of the UPEC infection model in mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca2+-dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial adherence to 5637 cells, the human bladder cell line, and the UPEC-induced cytotoxicity. In addition, pre-incubation of SP-D with 5637 cells resulted in the decreased adherence of UPEC to the cells and in the reduced number of the cells injured by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding. Consistent with the in vitro data, the exogenous administration of SP-D inhibited UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice. These results support the conclusion that SP-D can protect the bladder urothelium against UPEC infection, and suggest a possible function of SP-D in urinary tract.Journal of Biological Chemistry 09/2012; DOI:10.1074/jbc.M112.380287 · 4.60 Impact Factor
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ABSTRACT: Surfactant protein D (SP-D), a member of the C-type lectin (collectin) protein family, plays a critical role in innate host defence against various microbial pathogens and in the modulation of inflammatory responses in the lung. However, little is known about its expression and biological function in the kidney. In this work, we studied SP-D expression in human kidney and cultured human renal proximal tubular epithelial cells (HK-2), and examined the effect of SP-D on proinflammatory cytokine production after lipopolysaccharide (LPS) stimulus. We observed the expression of both SP-D mRNA and protein in human kidney and in-vitro HK-2 cells by immunohistochemistry, Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. To explore the potential role of SP-D in the pathogenesis of tubulointerstitial fibrosis in kidney infection, we examined the production of monocyte chemoattractant protein-1 (MCP-1) in HK-2 cells after LPS treatment. Results showed that the level of MCP-1 in the conditioned medium increased significantly when HK-2 cells were cultured with LPS (>0·1 µg/ml) for 8 h. Of interest, LPS treatment inhibited SP-D expression in HK-2 cells. Furthermore, over-expression of SP-D reduced significantly the LPS-induced expression of MCP-1 in transfected cells. These findings suggest that SP-D in the kidney functions as an anti-inflammatory factor in renal tubular epithelial cells and may modulate tubulointerstitial fibrosis in kidney.Clinical & Experimental Immunology 03/2012; 167(3):514-22. DOI:10.1111/j.1365-2249.2011.04521.x · 3.28 Impact Factor
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ABSTRACT: Pulmonary surfactant, a lipoprotein complex, maintains alveolar integrity and plays an important role in lung host defense, and control of inflammation. Altered inflammatory processes and surfactant dysfunction are well described events that occur in patients with acute or chronic lung disease that can develop secondary to a variety of insults. Genetic variants of surfactant proteins, including single nucleotide polymorphisms, haplotypes, and other genetic variations have been associated with acute and chronic lung disease throughout life in several populations and study groups. The hydrophilic surfactant proteins SP-A and SP-D, also known as collectins, in addition to their surfactant-related functions, are important innate immunity molecules as these, among others, exhibit the ability to bind and enhance clearance of a wide range of pathogens and allergens. This review focuses on published association studies of human surfactant proteins A and D genetic polymorphisms with respiratory, and non-respiratory diseases in adults, children, and newborns. The potential role of genetic variations in pulmonary disease or pathogenesis is discussed following an evaluation, and comparison of the available literature.Frontiers in Bioscience 01/2012; 17:407-29. DOI:10.2741/3935 · 4.25 Impact Factor