Enhanced uropathogenic Escherichia coli-induced infection in uroepithelial cells by sugar through TLR-4 and JAK/STAT1 signaling pathways

Ho, Chen Hsun; Fan, Chia Kwung; Wu, Chia Chang; Yu, Hong‐Jeng; Liu, Hsin Tien; Chen, Kuan Chou; Liu, Shih‐Ping; Cheng, Po Ching

doi:10.1016/j.jmii.2019.05.008

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…Our laboratory has verified that sugar enhances UPEC-induced bladder cell infection and inflammation by activating TLR-4- and JAK/STAT1-dependent pathways [ 26 ]. We recently demonstrated that insulin could reduce JAK/STAT-pathway-regulated UPEC infections in bladder cells in a high-glucose environment [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…AMP production is induced by the activation of the insulin-mediated PI3K/AKT pathway, eventually protecting urothelial cells from the invading UPEC [ 15 ]. We previously indicated that STAT1 and STAT3 in the JAK/STAT pathway play critical roles in the regulation of UPEC infection and colonization in uroepithelial cells, such as prostate or bladder cells, in high-glucose environments [ 26 , 27 , 30 ]. Therefore, it is necessary to understand the synergistic functions of AMP effects and JAK/STAT signaling pathway regulation in UPEC-infected bladder cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies in our laboratory also confirmed that an increase in the sugar concentration enhances UPEC-induced bladder cell inflammation. These responses were found to regulate the increase in UPEC infection of bladder cells by upregulating the mechanism of TLR-4 participation in the coordinated expansion of the media and JAK/STAT1 message transmission pathways [ 26 ]. We also showed that testosterone can effectively suppress the activation of the JAK/STAT1 signaling pathway, thereby suppressing UPEC’s invasion of prostate cells and inducing an inflammatory response [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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

Chen¹,

Fan

et al. 2022

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Chen¹,

Fan

et al. 2022

IJMS

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“…Among hormones, insulin has the ability to promote the secretion of RNase 7, RNase4, and LCN2, which are proven to be against bladder infection caused by a variety of uropathogens (167,168). In addition, insulin reduces the risk factor of blood sugar, (124,(169)(170)(171)(172)(173).. However, a prospective study showed that diabetic patients who used insulin for a long time had a higher risk of UTI than diabetic patients who did not use insulin.…”

Section: Regulation Of Hormonesmentioning

confidence: 99%

“…Among hormones, insulin has the ability to promote the secretion of RNase 7, RNase4, and LCN2, which are proven to be against bladder infection caused by a variety of uropathogens ( 167 , 168 ). In addition, insulin reduces the risk factor of blood sugar, thereby reducing the susceptibility of diabetic patients to bladder infection of UPEC, K.pneumoniae , E.faecalis , GBS, S.aureus , and Candida ( 124 , 169 – 173 ). .…”

Section: Potential Individual Immunomodulatory Interventionsmentioning

confidence: 99%

The immune responses to different Uropathogens call individual interventions for bladder infection

Yang

et al. 2022

Front. Immunol.

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Urinary tract infection (UTI) caused by uropathogens is the most common infectious disease and significantly affects all aspects of the quality of life of the patients. However, uropathogens are increasingly becoming antibiotic-resistant, which threatens the only effective treatment option available-antibiotic, resulting in higher medical costs, prolonged hospital stays, and increased mortality. Currently, people are turning their attention to the immune responses, hoping to find effective immunotherapeutic interventions which can be alternatives to the overuse of antibiotic drugs. Bladder infections are caused by the main nine uropathogens and the bladder executes different immune responses depending on the type of uropathogens. It is essential to understand the immune responses to diverse uropathogens in bladder infection for guiding the design and development of immunotherapeutic interventions. This review firstly sorts out and comparatively analyzes the immune responses to the main nine uropathogens in bladder infection, and summarizes their similarities and differences. Based on these immune responses, we innovatively propose that different microbial bladder infections should adopt corresponding immunomodulatory interventions, and the same immunomodulatory intervention can also be applied to diverse microbial infections if they share the same effective therapeutic targets.

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Mechanisms of Action for Diabetic Bladder Dysfunction — State of the Art

Powell

Gehring

2023

Curr Bladder Dysfunct Rep

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Purpose of Review Diabetes (DM) is a common cause of lower urinary tract symptoms (LUTS), known as diabetic bladder dysfunction (DBD). The phenotype for DBD is described in the literature with considerable heterogeneity and includes poor sensation, increased compliance, detrusor underactivity, urinary retention, weak stream, hesitancy, but also urgency incontinence, and, for many, detrusor overactivity. Progress has been made in understanding DBD, yet a unified phenotype or classification system for DBD remains elusive. Much remains unknown about the underlying mechanisms. Recent Findings No classification scheme to phenotype DBD has been proposed. Evidence from recent literature suggests four primary drivers: detrusor smooth muscle dysfunction, urothelial dysfunction, autonomic neurologic dysfunction, and circulating and systemic factors such as inflammation, oxidative stress, and microvascular damage. It is likely that these drivers have multi-factorial causes and inter-relate in complex ways. Recent findings in animal models lend new support to detrusor smooth muscle dysfunction as well as inflammation. Reports utilizing next-generation sequencing have begun to appear in the DBD literature and promise further insight. Summary DBD currently lacks a unified classification scheme and a clear mechanism. The advent of new, more translatable large animal models and next-generation sequencing promises many exciting new tools and models that more closely translate to human disease.

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Enhanced uropathogenic Escherichia coli-induced infection in uroepithelial cells by sugar through TLR-4 and JAK/STAT1 signaling pathways

Cited by 8 publications

References 39 publications

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

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

The immune responses to different Uropathogens call individual interventions for bladder infection

Mechanisms of Action for Diabetic Bladder Dysfunction — State of the Art

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