High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

Abstract

Abstract Objectives Recurrent urinary tract infections are associated with uropathogenic Escherichia coli ( UPEC ) ascending and infecting the urinary tract. Antibiotics provide only symptomatic relief, not prevent recurrence. Clinical evidence suggests that intravesical glycosaminoglycan therapy, such as hyaluronic acid ( HA ), helps reduce UTI recurrence. This has been investigated here using in vitro systems modelling the urogenital tract tissues. Methods RT 4 bladder cells were preconditioned with high molecular weight HA (> 1500 kDa) at 2 mg mL −1 and challenged with UPEC to analyse barrier protection and bacterial adherence. Untreated and HA ‐preconditioned VK 2 E6/E7 vaginal cells were challenged with E. coli flagellin (50 ng mL −1 ) to mimic bacterial challenge, and media analysed for lipocalin‐2, human β‐defensin 2 and interleukin‐8 by ELISA . Experiments were repeated after si RNA knockdown of Toll‐like receptors 2, 4 and 5, and CD 44 to investigate signalling. Results Microscopic analyses showed reduced bacterial adherence and urothelial disruption with HA , suggesting that HA functions as a barrier protecting the epithelium from bacterial infection. Cells treated with HA and flagellin simultaneously produced more of the host antimicrobial peptide LCN 2 and pro‐inflammatory IL ‐8 ( P < 0.05) compared to the no HA /flagellin challenges. Increased gene expression of DEFB 4 ( P < 0.05), but not the hBD 2 peptide, was observed in the HA /flagellin‐challenged cells. Conclusion These data suggest that exogenous HA has potential to protect the urogenital epithelia from UPEC infection via a two‐pronged approach that involves the physical enhancement of the epithelial barrier and augmentation of its innate immune response.