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Macrophage polarization switches during the course of inflammation along with the lipid mediators released. We investigated the lipid mediator formation in human monocyte-derived macrophages during in vitro differentiation and pathogen stimulation. For this, peripheral blood monocytes were differentiated into M1 (CSF-2/IFNγ) or M2 (CSF-1/IL-4) macrophages followed by stimulation with the toll-like receptor (TLR) ligands zymosan (TLR-2), Poly(I:C) (TLR-3) or bacterial lipopolysaccharides (TLR-4) mimicking fungal, viral and bacterial infection, respectively. Expression of enzymes involved in lipid mediator formation such as 5- and 15-lipoxygenases (LO), the 5-LO activating protein and cyclooxygenase-2 (COX-2) was monitored on mRNA and protein level and lipid mediator formation was assessed. In addition, cytokine release was measured. In vitro differentiation of human peripheral blood monocytes to M1 and M2 macrophages considerably attenuated 5-LO activity. Furthermore, while TLR-2 and -4 stimulation of M1 macrophages primarily triggered pro-inflammatory cytokines and lipid mediators, persistent stimulation (16 h) of human M2 macrophages induced a coordinated upregulation of 5- and 15-LO-2 expression. This was accompanied by a marked increase in IL-10 and monohydroxylated 15-LO products in the conditioned media of the cells. After additional stimulation with Ca ionophore combined with supplementation of arachidonic, eicosapentaenoic and docosahexaenoic acid these cells also released small amounts of SPM such as lipoxins and resolvins. From this we conclude that activation of TLR-2 or -4 triggers the biosynthesis of pro-inflammatory 5-LO and COX-2 derived lipid mediators in human monocyte-derived M1 macrophages while persistent stimulation of M2 macrophages induces a shift towards pro-resolving 15-LO derived oxylipins.
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http://dx.doi.org/10.1016/j.bbalip.2020.158702 | DOI Listing |
Front Immunol
December 2024
School of Pharmacy, Changchun University of Traditional Chinese Medicine, Changchun, China.
Asthma, is a common, significant and diverse condition marked by persistent airway inflammation, with a major impact on human health worldwide. The predisposing factors for asthma are complex and widespread. The beneficial effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in asthma have increasingly attracted attention recently.
View Article and Find Full Text PDFInfect Drug Resist
December 2024
School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China.
Sepsis is a complicated clinical disease caused by a defective host response to infection, leading to elevated morbidity and fatality globally. Sepsis patients have a significant risk of life-threatening organ damage, including hearts, brains, lungs, kidneys, and livers. Nevertheless, the molecular pathways driving organ injury in sepsis are not well known.
View Article and Find Full Text PDFEClinicalMedicine
January 2025
Department of Epidemiology, NHC Key Laboratory for Health Technology Assessment, Fudan University School of Public Health, 138 Yi Xue Yuan Road, Shanghai, 200032, China.
Background: Depression is a severe mental disorder commonly co-morbid with diabetes, but it remains to elucidate whether depression is associated with the risks of a wide range of vascular complications in people with type 2 diabetes mellitus (T2DM) and whether metabolic biomarkers may mediate this pathway.
Methods: We conducted this prospective analysis among the participants of the UK Biobank who were diagnosed with T2DM and free of vascular complications at baseline between March 13, 2006 and September 30, 2010. Major depressive disorder (MDD) was ascertained according to the hospital admission records and self-report of doctor-diagnosed conditions, while the presence of depressive symptoms was assessed using the Patient Health Questionnaire-2.
iScience
December 2024
Poltava State Medical University, Department of Pathophysiology, Poltava, Ukraine.
5-Aminolevulinic acid (5-ALA) is an essential compound in the biosynthesis of heme, playing a critical role in various physiological processes within the human body. This review provides the thorough analysis of the latest research on the molecular mechanisms and potential therapeutic benefits of 5-ALA in managing metabolic disorders. The ability of 5-ALA to influence immune response and inflammation, oxidative/nitrosative stress, antioxidant system, mitochondrial functions, as well as carbohydrate and lipid metabolism, is mediated by molecular mechanisms associated with the suppression of the transcription factor NF-κB signaling pathway, activation of the transcription factor Nrf2/heme oxygenase-1 (HO-1) system leading to the formation of heme-derived reaction products (carbon monoxide, ferrous iron, biliverdin, and bilirubin), which may contribute to HO-1-dependent cytoprotection through antioxidant and immunomodulatory effects.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Shenzhen Hospital (Futian), Guangzhou University of Chinese Medicine, Shenzhen, China.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance (IR) and insufficient insulin secretion. Its characteristic pathophysiological processes involve the interaction of multiple mechanisms. In recent years, globally, the prevalence of T2DM has shown a sharp rise due to profound changes in socio-economic structure, the persistent influence of environmental factors, and the complex role of genetic background.
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