Dataset Information

HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.

ABSTRACT: Infections are common in patients with diabetes, but increasing antibiotic resistance hampers successful bacterial clearance and calls for alternative treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is known to influence the innate immune defense and could therefore serve as a possible target. However, the impact of high glucose on HIF-1 has received little attention and merits closer investigation. Here, we show that higher levels of proinflammatory cytokines and CAMP, encoding for the antimicrobial peptide cathelicidin, LL-37, correlate with HIF-1 in type 2 diabetic patients. Chemical activation of HIF-1 further enhanced LL-37, IL-1β, and IL-8 in human uroepithelial cells exposed to high glucose. Moreover, HIF-1 activation of transurethrally infected diabetic mice resulted in lower bacterial load. Drugs activating HIF-1 could therefore in the future potentially have a therapeutic role in clearing bacteria in diabetic patients with infections where antibiotic treatment failed. KEY MESSAGES: • Mohanty et al. "HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients." • Our study highlights induction of the antimicrobial peptide, LL-37, and strengthening of the innate immunity through hypoxia-inducible factor 1 (HIF-1) in diabetes. • Our key observations are: 1. HIF-1 activation increased LL-37 expression in human urothelial cells treated with high glucose. In line with that, we demonstrated that patients with type 2 diabetes living at high altitude had increased levels of the LL-37. 2. HIF-1 activation increased IL-1β and IL-8 in human uroepithelial cells treated with high glucose concentration. 3. Pharmacological activation of HIF-1 decreased bacterial load in the urinary bladder of mice with hereditary diabetes. • We conclude that enhancing HIF-1 may along with antibiotics in the future contribute to the treatment in selected patient groups where traditional therapy is not possible.

SUBMITTER: Mohanty S

PROVIDER: S-EPMC8724101 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundVitamin D insufficiency is common in industrialized and developing nations. Recent studies have shown that vitamin D insufficiency is associated with a higher risk of active tuberculosis. Laboratory studies provided a mechanism for this link on the basis of findings that vitamin D metabolites regulate the expression of cathelicidin (LL-37), which is an endogenous antimicrobial peptide with activity against Mycobacterium tuberculosis. Little information is available on the clinical relation between vitamin D, LL-37 concentrations, and disease severity in patients with tuberculosis.ObjectiveThe primary objective of the study was to evaluate the relation between vitamin D nutriture, serum LL-37 concentrations, and tuberculosis by using samples stored in the Tuberculosis Trials Consortium serum repository.DesignWe measured 25-hydroxyvitamin D [25(OH)D] and LL-37 concentrations in 95 serum specimens from patients with culture-confirmed pulmonary tuberculosis and correlated these concentrations to clinical and demographic variables.ResultsThe prevalence of vitamin D insufficiency [serum 25(OH)D concentration lt 30 ng/mL] in patients with active tuberculosis was 86% (n = 95) with a mean baseline serum 25(OH)D concentration of 20.4 ng/mL. Factors associated with vitamin D insufficiency were black race and indoor lifestyle. The mean ( plusmn SD) baseline LL-37 concentration was 49.5 plusmn 23.8 ng/mL. Higher LL-37 concentrations correlated with acid fast bacilli sputum smear positivity and weight gt 10% below ideal body weight. Serum vitamin D status of the study subjects did not correlate with serum LL-37 concentrations.ConclusionMore prospectively designed studies are needed to evaluate the clinical implications of vitamin D insufficiency in patients with tuberculosis and the utility of circulating LL-37 as a potential biomarker in patients with active tuberculosis disease. The parent trial was registered at clinicaltrials.gov as NCT00023335.

Dataset Information

HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets