Antimicrobial Peptide LCN2 Inhibited Uropathogenic Escherichia coli Infection in Bladder Cells in a High-Glucose Environment through JAK/STAT Signaling Pathway

Abstract

JAK/STAT plays a key role in regulating uropathogenic Escherichia coli (UPEC) infection in urothelial cells, probably via antimicrobial peptide (AMP) production, in diabetic patients with urinary tract infections. Whether multiple pathways regulate AMPs, especially lipid-carrying protein-2 (LCN2), to achieve a vital effect is unknown. We investigated the effects of an LCN2 pretreatment on the regulation of the JAK/STAT pathway in a high-glucose environment using a bladder cell model with GFP-UPEC and phycoerythrin-labeled TLR-4, STAT1, and STAT3. Pretreatment with 5 or 25 μg/mL LCN2 for 24 h dose-dependently suppressed UPEC infections in bladder cells. TLR-4, STAT1, and STAT3 expression were dose-dependently downregulated after LCN2 pretreatment. The LCN2-mediated alleviation of UPEC infection in a high-glucose environment downregulated TLR-4 and the JAK/STAT transduction pathway and decreased the UPEC-induced secretion of exogenous inflammatory interleukin (IL)-6 and IL-8. Our study provides evidence that LCN2 can alleviate UPEC infection in bladder epithelial cells by decreasing JAK/STAT pathway activation in a high-glucose environment. LCN2 dose-dependently inhibits UPEC infection via TLR-4 expression and JAK/STAT pathway modulation. These findings may provide a rationale for targeting LCN2/TLR-4/JAK/STAT regulation in bacterial cystitis treatment. Further studies should explore specific mechanisms by which the LCN2, TLR-4, and JAK/STAT pathways participate in UPEC-induced inflammation to facilitate the development of effective therapies for cystitis.

PCLLA-nanoHA Bone Substitute Promotes M2 Macrophage Polarization and Improves Alveolar Bone Repair in Diabetic Environments

“…This enhanced effect of PCLLA-nanoHA may be attributed to its increased degradability, leading to the release and exposure of HA components, such as calcium and phosphate ions [39,40], which are known to activate downstream signaling pathways, including the JAK-STAT, PI3K-Akt pathways, and mitochondrial pathways [41,42]. However, further investigation is needed to elucidate the specific mechanisms by which ions directly regulate macrophages function and how leptin protein responds to ions, ultimately influencing macrophages fate.…”