Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (TH1)-TH17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor.

Irf5 promotes inflammatory macrophage polarization and th1/th17 response

A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.

Nature and mental health: An ecosystem service perspective.

People from all ethnic backgrounds spend some of their leisure time in green areas. This study found that urban parks are more inclusive green places than non-urban green areas, and that urban parks can promote social cohesion. The objective of the research was to establish the extent to which urban parks facilitate social cohesion and how social interaction and place attachment can contribute to such cohesion. Quantitative research (a survey) and qualitative research (observations and interviews) carried out in five urban parks in the Netherlands revealed that there are many similarities in the ways that ethnic groups use urban parks and in the meanings of such parks to these groups. Urban parks are sites where different ethnic groups mingle and where informal and cursory interactions can stimulate social cohesion. Furthermore, being involved and concerned with parks can facilitate attachment to these places. Urban parks can provide a vital locality where everyday experiences are shared and negotiated with a variety of people. The design of a park, its location and people's image of the park in combination with the cultural characteristics of various ethnic groups inform the opportunities for intercultural interactions.

Social interactions in urban parks: stimulating social cohesion?

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/233228/Bush_Doyon_Building urban resilience_1-s2.0-S0264275119313976-main.pdf

Building urban resilience with nature-based solutions: How can urban planning contribute?

As our behavioral patterns change due to the COVID-19 crisis, our impact on nature and the environment changes too. Pollution levels are showing significant reductions. People are more aware of the importance of access to local green and blue spaces. By analyzing online search behavior in twenty European countries, we investigate how public awareness of nature and the environment has evolved during the COVID-19 crisis. We find that the crisis goes hand in hand with a positive shift in public awareness of nature-related topics, but that awareness of environmental topics remains unaffected. While the decreasing pollution levels and media attention may reduce the overall sense of urgency to tackle pollution problems, the increased experience with local natural resources may strengthen public support for a recovery program that puts the transition towards a more sustainable economic system centrally.

/pdf/public-awareness-of-nature-and-the-environment-during-the-luv5kqp6z3.pdf

Public Awareness of Nature and the Environment During the COVID-19 Crisis.

Social cohesion involves the interpersonal dynamics and sense of connection among people. Increased social cohesion can be associated with various physical and psychological health benefits. The presence of urban green spaces can encourage positive social interactions that cultivate social cohesion in ways that enhance health and well-being. Urban green spaces have also been linked to positive health behaviors and outcomes including increased physical activity and social engagement. Understanding the relationship between social cohesion and urban green space is important for informing holistic approaches to health. In this article, we discuss how positive interactions in urban green space can catalyze social cohesion, social capital and critical health-promoting behaviors that may enhance psychological health and well-being. We also summarize the strengths and limitations of previous studies and suggest directions for future research.

https://www.mdpi.com/1660-4601/16/3/452/pdf

The Relationship between Social Cohesion and Urban Green Space: An Avenue for Health Promotion.

Interferon regulatory factor 5 (IRF5) has been called a "master switch" for its ability to determine whether cells mount proinflammatory or anti-inflammatory responses. Accordingly, IRF5 should be an attractive target for therapeutic drug development. Here we report on the development of a novel decoy peptide inhibitor of IRF5 that decreases myocardial inflammation and improves vascular endothelial cell (EC) function in tight-skin (Tsk/+) mice. Biolayer interferometry studies showed the Kd of IRF5D for recombinant IRF5 to be 3.72 ± 0.74x10-6M. Increasing concentrations of IRF5D (0-100 μg/mL, 24h) had no significant effect on EC proliferation or apoptosis. Treatment of Tsk/+ mice with IRF5D (1mg/kg/d subcutaneously, 21d) reduced IRF5 and ICAM-1 expression and monocyte/macrophage and neutrophil counts in Tsk/+ hearts compared to expression in hearts from PBS-treated Tsk/+ mice (p<0.05). EC-dependent vasodilatation of facialis arteries isolated from PBS-treated Tsk/+ mice was reduced (~15%). IRF5D treatments (1mg/kg/d, 21d) improved vasodilatation in arteries isolated from Tsk/+ mice nearly 3-fold (~45%, p<0.05), representing nearly 83% of the vasodilatation in arteries isolated from C57Bl/6J mice (~55%). IRF5D (50μg/mL, 24h) reduced nuclear translocation of IRF5 in myocytes cultured on both Tsk/+ cardiac matrix and C57Bl/6J cardiac matrix (p<0.05). These data suggest that IRF5 plays a causal role in inflammation, fibrosis and impaired vascular EC function in Tsk/+ mice and that treatment with IRF5D effectively counters IRF5-dependent mechanisms of inflammation and fibrosis in the myocardium in these mice.

/pdf/an-irf5-decoy-peptide-reduces-myocardial-inflammation-and-3hbgtnczdj.pdf

An IRF5 Decoy Peptide Reduces Myocardial Inflammation and Fibrosis and Improves Endothelial Cell Function in Tight-Skin Mice

BACKGROUND Intralipid (ILP), a lipid emulsion, protects organs against ischemia/reperfusion (IR) injury. We hypothesized that ILP activates endothelial nitric oxide synthase (eNOS) and increases NO release from endothelial cells (ECs) through a fatty-acid translocase cluster of differentiation (CD36) mediated endocytotic mechanism, acting as a potentially protective paracrine signal during oxidative stress. METHODS Human umbilical-vein ECs were exposed to 1% ILP for 2 hours followed by oxidative stress with 0.2-mM hydrogen peroxide for 2 hours. Western blots were conducted with anti-CD36, dynamin-2, src-kinase-1, eNOS, and phospho-eNOS; equal protein loading was confirmed with β-actin. CD36 immunoprecipitation was probed for caveolin-1 to determine if CD36 and caveolin-1 were complexed on the cell membrane. NO was measured by fluorescence of ECs. RESULTS ILP caused a 227% increase in CD36 expression vs controls. Immunoprecipitation indicated a CD36/caveolin-1 complex on ECs' membrane with exposure to ILP. Dynamin-2 increased 52% and src-kinase-1 340% after ILP treatment vs control cells. eNOS phosphorylation was confirmed by a 63% increase in the phospho-eNOS/eNOS ratio in ILP-treated cells, and NO fluorescence increased 102%. CONCLUSION ILP enters ECs via endocytosis by a CD36/caveolin-1 cell membrane receptor complex, which in turn is pulled into the cell by dynamin-2 activity. Upregulation of src-kinase-1 and eNOS phosphorylation suggest downstream mediators. Subsequent NO release from ECs serve as a paracrine signal to neighboring cells for protection against IR injury. Student t-test was utilized for single comparisons and analysis of variance with Bonferroni-Dunn post hoc modification for multiple comparisons; P < .05 was considered statistically significant.

Omoshalewa Bamkole

Papers

The Relationship between Social Cohesion and Urban Green Space: An Avenue for Health Promotion.

An IRF5 Decoy Peptide Reduces Myocardial Inflammation and Fibrosis and Improves Endothelial Cell Function in Tight-Skin Mice

Intralipid Increases Nitric Oxide Release from Human Endothelial Cells During Oxidative Stress