Abstract
Background: Human antibacterial peptides play a crucial role in maintenance of normal bacterial flora and in fighting pathogens as parts of innate immune defence. The human cathelicidin (LL-37) has been studied mainly in blood cells and epithelium of skin, respiratory and gastrointestinal tracts. In the present study, we sought to investigate LL-37 expression in human urinary tract and its role during bacterial urinary tract infection (UTI).
Methods: Urine of 28 healthy children was analysed by LL-37 ELISA, as well as urine of 29 children during acute phase of UTI. Healthy kidney tissue from 11 patients nephrectomised due to renal cancer was examined using ELISA, Taqman real-time PCR and immunohistochemistry. In addition, kidneys from healthy mice and mice transurethraly infected with E.coli were analysed immunohistochemicaly for mouse cathelicidin (CRAMP). The expression of LL-37 mRNA was studied in 6 different human renal epithelial and uroepithelial cell lines, both cancer-derived and normal, and also after stimulation with uropathogenic E.coli.
Results: Low levels of cathelicidin were found in the urine of healthy children (0.313 ng/ml, range 0.194 to 5.944) as well as in healthy renal tissue (51.590 ng/ìg tissue, range 20.725 to 102.355). By immunohistochemistry, cathelicidin could be localised mainly to the cytoplasm of renal tubular cells. Upon urinary tract infection, urinary levels of cathelicidin significantly increased (2.353 ng/ml, range 0.133 to 312.5, p<0.001, Mann-Whitney U test) and were correlated with the urine leukocyte levels (R=0.60, p<0.001, Spearman rank correlation test). Correspondingly, immunohistochemical staining of infected mice showed cathelicidin mainly in the cytoplasm of invading leukocytes. mRNA for LL-37 was present in the pieces of renal cortex and pelvis renalis, and also in renal epithelial and uroepithelial cell lines. After stimulation with uropathogenic E.coli, LL-37 mRNA in all studied cell lines significantly decreased by 38 to 64% (p<0.01, respectively, Mann-Whitney U test).
Conclusion: Our results indicate that cathelicidin LL-37 is expressed in human renal tubular and uroepithelial cells. During bacterial infection, invading leukocytes produce substantial amounts of LL-37. In renal tubular and uroepithelial cells, on the other hand, the constitutive production of LL-37 seems to be suppressed by E.coli, which could be a pathogenic mechanism promoting bacterial establishment within urinary tract.
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Chromek, M., Agerberth, B., Ehrén, I. et al. 51 The Human Cathelicidin: Another Antimicrobial Peptide of Urinary Tract. Pediatr Res 56, 472 (2004). https://doi.org/10.1203/00006450-200409000-00074
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DOI: https://doi.org/10.1203/00006450-200409000-00074