Antimicrobial peptides (AMPs), which are natural
antibiotics, protect against pathogens invading the urinary tract.
RNase 7 with antimicrobial properties has rapid and powerful suppressive effects against Gram-positive and
Gram-negative bacterial infections. However, its detailed antibacterial mechanisms have not been fully determined. Here, we investigate whether
RNase 7 had an impact on bladder cells under uropathogenic Escherichia coli (UPEC)
infection in a high-
glucose environment using in vitro GFP-UPEC-infected bladder cell and PE-labeled TLR4, STAT1, and STAT3 models. We provide evidence of the suppressive effects of
RNase 7 on UPEC
infection and UPEC-induced inflammatory responses by regulating the JAK/STAT signaling pathway using
JAK inhibitor and STAT inhibitor blocking experiments. Pretreatment with different concentrations of
RNase 7 for 24 h concentration-dependently suppressed UPEC invasion in bladder cells (5 μg/mL reducing 45%; 25 μg/mL reducing 60%). The expressions of TLR4, STAT1, and STAT3 were also downregulated in a concentration-dependent manner after
RNase 7 pretreatment (5 μg/mL reducing 35%, 54% and 35%; 25 μg/mL reducing 60%, 75% and 64%, respectively).
RNase 7-induced decrease in UPEC
infection in a high-
glucose environment not only downregulated the expression of TLR4
protein and the JAK/STAT signaling pathway but also decreased UPEC-induced secretion of exogenous inflammatory
IL-6 and
IL-8 cytokines, although
IL-8 levels increased in the 25 μg/mL
RNase 7-treated group. Thus, inhibition of STAT affected pSTAT1, pSTAT3, and TLR4 expression, as well as proinflammatory
IL-6 and IFN-γ expression. Notably, blocking JAK resulted in the rebound expression of related
proteins, especially pSTAT1, TLR4, and
IL-6. The present study showed the suppressive effects of
RNase 7 on UPEC
infection and induced
inflammation in bladder epithelial cells in a high-
glucose environment.
RNase 7 may be an anti-inflammatory and anti-infective mediator in bladder cells by downregulating the JAK/STAT signaling pathway and may be beneficial in treating
cystitis in DM patients. These results will help clarify the correlation between
AMP production and UTI, identify the relationship between
urinary tract infection and diabetes in UTI patients, and develop novel diagnostics or possible treatments targeting
RNase 7.