Protectin

Rheumatoid arthritis (RA) is typified by persistent joint inflammation, which leads to the deterioration of bone and cartilage and a reduction in overall quality of life. The global prevalence of pain as a primary symptom in RA is influenced by the interplay between inflammation and its resolution. The identification of a family of lipid mediators known as specialized pro-resolving mediators (SPM)s has contributed to the progress of our comprehension of inflammatory conditions. SPMs have been observed to trigger the process of inflammation resolution, thereby reinstating the homeostasis of the inflammatory response...

Evidence for the biosynthetic pathways of the specialized pro-resolving mediator (SPM) protectin D1 (PD1) and its biochemical further local metabolism were presented during the 8th European Workshop on Lipid Mediators, organized June 29th -July 1st , 2022, in Stockholm, Sweden. Herein, we provide an extended and detailed discussion of these topics. PD1, one of 43 SPMs reported so far, exhibits very potent pro-resolution and anti-inflammatory bioactions. Many research groups worldwide have confirmed these and other interesting bioactions...

Endogenous inhibitory mechanisms promote resolution of inflammation, enhance tissue repair and integrity, and promote homeostasis in the lung. These mechanisms include steroid hormones, regulatory T cells, IL-10, prostaglandin E2 , prostaglandin I2 , lipoxins, resolvins, protectins, maresins, glucagon-like peptide-1 receptor, adrenomedullin, nitric oxide, and carbon monoxide. Here we review the most recent literature regarding these endogenous inhibitory mechanisms in asthma, which remain a promising target for the prevention and treatment of asthma...

COVID-19 is caused by SARS-CoV-2 infection. Epithelial and T, NK, and other immunocytes release bioactive lipids especially arachidonic acid (AA) in response to microbial infections to inactivate them and upregulate the immune system. COVID-19 (coronavirus) and other enveloped viruses including severe acute respiratory syndrome (SARS-CoV-1 of 2002-2003) and Middle East respiratory syndrome (MERS; 2012-ongoing) and hepatitis B and C (HBV and HCV) can be inactivated by AA, γ-linolenic acid (GLA, dihomo-GLA (DGLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), which are precursors to several eicosanoids...

Atopic dermatitis (AD) is a chronic inflammatory skin condition that primarily results from immune dysregulation. We determined the potential therapeutic benefits of lipid mediators (LM, 17S-monohydroxy DHA, resolvin D5, and protectin DX in a ratio of 3:47:50) produced by soybean lipoxygenase from DHA. The underlying molecular mechanisms involved in TNF-α/IFN-γ-stimulated HaCaT cells as well as its effect in an AD mouse model induced by DNCB in BALB/c mice were examined. The results indicated that LM effectively attenuates the production of inflammatory cytokines (IL-6 and IL-1β) and chemokines (IL-8 and MCP-1) by inhibiting the NF-κB signaling pathway in TNF-α/IFN-γ-stimulated HaCaT cells...

BACKGROUND: Tracheal intubation in critically ill patients remains high-risk despite advances in equipment, technique, and clinical guidelines. Many patients with COVID-19 were in respiratory distress and required intubation that is considered an aerosol-generating procedure (AGP). The transition to videolaryngoscopy as a routine first line option throughout anesthetic and ICU practice has been reported. We evaluated the ease of intubation, success rate, use of accessory maneuvers and adverse outcomes during and 24 hours after intubation with the McGrath videolaryngoscope...

Myocardial ischemia/reperfusion (I/R) injury after the onset of acute myocardial infarction (AMI) can be life-threatening, and there is no effective strategy for therapeutic intervention. Here, we studied the potential of protectin D1 in protecting from I/R-induced cardiac damages and investigated the underlying mechanisms. An in vivo rat model of I/R after AMI induction was established through the ligation of the left anterior descending (LAD) artery to assess the cardiac functions and evaluate the protective effect of protectin D1...

Docosahexaenoic acid (C22:6 n -3, DHA) is the precursor of specialized pro-resolving lipid mediators (SPMs), such as resolvin, protectin, and maresin families which have been considered therapeutic bioactive compounds for human health. Growing evidence indicates that DHA and SPMs are beneficial strategies in the amelioration, regulation, and duration of inflammatory processes through different biological actions. The present review discusses the reported therapeutic benefits of SPMs on various diseases and their potential clinical applications...

OBJECTIVES: Cardiovascular disease (CVD) and periodontal disease have a common pathogenesis with inflammation and resolution steps. Although the relationships among periodontal disease, CVD, and specialized pro-resolving lipid mediator (sPRLM)s are well known, there is no study about the combined effects of cardiovascular and periodontal treatments on sPRLM levels. It was aimed to evaluate the effects of periodontal and cardiovascular therapies on sPRLMs (lipoxin A4, protectin (PD)1, resolvin (Rv) E1, RvD1, and maresin (MaR)1) in patients with CVD and periodontal disease...

Escherichia coli is the main cause of urinary tract infections (UTI). While genomic comparison of specific clones recovered from animals, and human extraintestinal infections show high identity, studies demonstrating the uropathogenicity are lacking. In this study, comparative genomics combined with bladder-cell and biofilm formation assays, were performed for 31 E. coli of different origins: 7 from meat (poultry, beef, and pork); 2 from avian-farm environment; 12 from human uncomplicated UTI, uUTI; and 10 from human complicated UTI, cUTI...

The resolution of inflammation is an essential endogenous process that protects host tissues from an exaggerated chronic inflammatory response. Multiple interactions between host cells and resident oral microbiome regulate the protective functions that lead to inflammation in the oral cavity. Failure of appropriate regulation of inflammation can lead to chronic inflammatory diseases that result from an imbalance between pro-inflammatory and pro-resolution mediators. Thus, failure of the host to resolve inflammation can be considered an essential pathological mechanism for progression from the late stages of acute inflammation to a chronic inflammatory response...

Non-resolving inflammation is an underpinning of cardiovascular diseases including atherosclerosis. The resolution of inflammation is an active and highly coordinated process that involves the generation of specialized pro-resolving mediators (SPMs), and other factors including proteins, gases, and nucleotides. SPMs comprise a superfamily of lipid mediators that includes lipoxins, resolvins, maresins and protectins. SPMs act through distinct G protein-coupled receptors (GPCRs) and have been extensively studied in animal models of cardiovascular diseases...

Fucoidans from brown algae are described as anti-inflammatory, antioxidative, and antiangiogenic. We tested two Saccharina latissima fucoidans (SL-FRO and SL-NOR) regarding their potential biological effects against age-related macular degeneration (AMD). Primary porcine retinal pigment epithelium (RPE), human RPE cell line ARPE-19, and human uveal melanoma cell line OMM-1 were used. Cell survival was assessed in tetrazolium assay (MTT). Oxidative stress assays were induced with erastin or H2 O2 . Supernatants were harvested to assess secreted vascular endothelial growth factor A (VEGF-A) in ELISA...

We report a gram-scale total synthesis of protectin DX (PDX) following a convergent synthetic route (24 steps) from l-malic acid. This novel synthetic strategy is based on the assembly of three main building blocks using a Sonogashira coupling reaction (blocks A and B) and Wittig olefination (block C) to provide the 22-carbon backbone of PDX. A key stereoselective reduction of enediyne leads to a central E , Z , E -trienic system of PDX and also gives access to its labeled versions (D and T).

INTRODUCTION: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models...

Age-related macular degeneration (AMD) is a multifactorial disease in which angiogenesis, oxidative stress and inflammation are important contributing factors. In this study, we investigated the anti-inflammatory effects of a fucoidan from the brown algae Fucus vesiculosus (FV) in primary porcine RPE cells. Inflammation was induced by lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly I:C), Pam2CSK4 (Pam), or tumor necrosis factor alpha (TNF-α). Cell viability was tested with thiazolyl blue tetrazolium bromide (MTT) test, barrier function by measuring transepithelial electric resistance (TEER), interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion in ELISA, retinal pigment epithelium-specific 65 kDa protein (RPE65) and protectin (CD59) expression in Western blot, gene expression with quantitative polymerase chain reaction (qPCR) ( IL6 , IL8 , MERTK , PIK3CA ), and phagocytotic activity in a microscopic assay...

BACKGROUND: Acute lung injury (ALI) is a common and serious complication of sepsis with high mortality. Ferroptosis, categorized as programmed cell death, contributes to the development of lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is an endogenous lipid mediator that exerts protective effects against multiorgan injury. However, the role of PCTR1 in the ferroptosis of sepsis-related ALI remains unknown. METHODS: A pulmonary epithelial cell line and a mouse model of ALI stimulated with lipopolysaccharide (LPS) were established in vitro and in vivo...

The implantation of a biomaterial will lead to the immediate onset of an acute inflammatory response, which is of key importance in shaping the quality of the repair process. However, the return to homeostasis is critical to prevent a chronic inflammatory response that may impair the healing process. The resolution of the inflammatory response is now recognized as an active and highly regulated process, being described as specialized immunoresolvents that have a fundamental role in the termination of the acute inflammatory response...

Frailty in aging is driven by the dysregulation of multiple biological pathways. Protectin DX (PDX) is a docosahexaenoic acid (DHA)-derived molecule that alleviates many chronic inflammatory disorders, but its potential effects on frailty remain unknown. Our goal is to identify age-related impairments in metabolic systems and to evaluate the therapeutic potential of PDX on frailty, physical performance, and health parameters. A set of 22-month-old C57BL/6 male and female mice were assigned to vehicle (Old) or PDX daily gavage treatment for 9 weeks, whereas 6-month-old (Adult) mice received only vehicle...

Persistent skin inflammation and impaired resolution are the main contributors to psoriasis and associated cardiometabolic complications. Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to exert beneficial effects on inflammatory response and lipid function. However, a specific role of omega-3 PUFAs in psoriasis and accompanied pathologies are still a matter of debate. Here, we carried out a direct comparison between EPA and DHA 12 weeks diet intervention treatment of psoriasis-like skin inflammation in the K14-Rac1V12 mouse model...