Expression of TREM-1 is inhibited by PGD2 and PGJ2 in macrophages.

TREM-1 is a superimmunoglobulin receptor present on neutrophils and monocytes, which plays an important role in the amplification of inflammation. The natural ligands for TREM-1 have not been identified; however, Toll-like receptor ligands are known to induce the expression of TREM-1. Blockade of TREM-1 has shown to improve survival in animal models of sepsis. In the present studies, we investigated the role of lipid mediators in the expression of TREM-1. In a macrophage cell line, we show that the expression of TREM-1 in response to LPS and bacteria Pseudomonas aeruginosa is inhibited by PGD(2) and cyclopentanone prostaglandins PGJ(2) and 15-dPGJ(2). The inhibition of TREM-1 by these prostaglandins is independent of the PGD(2) receptors and PPARγ but occurs by activation of Nrf2 and inhibition of NF-κB. Our data suggest a novel mechanism by which these prostaglandins exhibit anti-inflammatory effects and a new therapeutic approach to inhibition of TREM-1.

Prospective exploration of the effect of adiposity and associated microbial factors on healing and progression of diabetic foot ulcers in Tanzania: study protocol of a longitudinal cohort study.

BACKGROUND: Diabetic foot ulcers (DFUs) are associated with high morbidity and mortality in low-income countries. This coexists with an increasing prevalence of obesity which has been reported to alter antimicrobial susceptibility and potentially affect the outcome of infected foot ulcers. This study aims to determine whether adiposity and local microbial factors affect the progression and healing of foot ulcers in people with type 2 diabetes in hospital settings in Tanzania. METHODS AND ANALYSIS: A prospective cohort of 300 individuals with type 2 diabetes presenting with DFUs at an outpatient clinic will be enrolled into the study. At baseline, participants will be stratified into normal and high adiposity groups (150 per group) as measured by bioelectrical impedance analysis (BIA). Both groups will receive DFU management according to locally appropriate standards of care and will be followed up for 24 weeks or until complete wound healing, whichever occurs first. The primary end point is complete wound healing at 24 weeks while secondary end points are ulcer progression (worsening or improving), amputation and death. Enrolling 150 participants per group will have a minimum power of 80% to detect a 20% difference in cumulative incidence of complete ulcer healing (at the 5% level of statistical significance) between the normal and high adiposity groups. ETHICAL CONSIDERATIONS AND DISSEMINATION OF RESULTS: This study will be conducted in compliance with the independent institutional review boards (IRBs), informed consent guidelines, the declaration of Helsinki and International Conference on Harmonisation, Good Clinical Practice Guidelines. Ethical clearance has been granted by the Muhimbili University of Health and Allied Sciences ethical review board (MUHAS Ref. No. DA.282/298/01 .C/). Permissions to conduct the study have been granted by the Abbas Medical Centre and the Muhimbili Academic Medical Centre (MAMC).Progress and results emanating from this work will be communicated to the scientific community through conference presentations, short communications (using journal letters and interesting case reports) and peer-reviewed publications. When necessary, through proper channels, popular means of communication (newspapers, magazines and online communications) will be used to inform policy and the public. TRIAL REGISTRATION NUMBER: NCT03960255; Pre-results.