The Atlas of Inflammation-Resolution (AIR)

Abstract

Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi and interdisciplinary approach necessary. This Atlas of Inflammation Resolution (AIR) is a web-based resource capturing the state-of-theart in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. The AIR serves as an open access knowledgebase, including a gateway to numerous public databases. It is furthermore possible for the user to map experimental data onto the molecular interaction maps of the AIR, providing the basis for bioinformatics analyses and systems biology approaches. By mapping experimental data onto the Atlas, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards.The Atlas of Inflammation Resolution was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses. Abbreviations:

Lipid mediator profile of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators during the first seven days

“…[20] Further investigation of their activity may give more detailed insights into the way that external application of ω3-FA contributes to wound healing. In light of the trans cellular synthesis pathways required to generate these compounds [22] the results imply that immune cell recruitment into wounds treated with FSG is different than in non-FSG treated wounds. A more detailed immunological investigation focusing on white blood cells and cytokines would however be required to confirm this.…”

“…FSG contain high amounts of EPA and DHA but their direct involvement in the biochemical processes of wound healing has not been demonstrated. Based on the biological properties of EPA and DHA previously described in the literature [21,22] we hypothesized that the two ω3-FA might affect the resolution of inflammation or other relevant wound healing stages through the formation of lipid mediators. In our study, we monitored the profiles of approximately 60 known lipid mediators with primarily pro-antiand resolving inflammation properties.…”

“…[24] In the analyzed biopsies however, RvD1 as well as all the other measured SPMs (e.g., RvE1, RvE2, RvE3, RvD2, 7S-MaR1, PD1, and PDX) were not detected in any of the conditions. The absence of these compounds might be associated with the fact their formation is associated with the very early stages of the resolution of inflammation, [22] that are prior to the day that our first biopsy was collected. A much denser sampling during the first hours to days should be mandatory in order to exclude the formation of this compounds.…”

Prostanoids and Resolution of Inflammation – Beyond the Lipid-Mediator Class Switch

“…Moreover, while the pro-resolving activity of cyclooxygenase metabolites has long been attributed predominantly to PGD 2 and 15d-PGJ 2 (124), PGE 2 emerged as an important facilitator of the lipid-mediator class switch inducing not only the production of PGD 2 and its derivatives, but also of the so-called specialized pro-resolving mediators (SPM) (20). SPM, synthesized by 15-lipoxygenase (ALOX15) (31,(125)(126)(127), are key players in the resolution of inflammation (114,128). PGE 2 induces the expression of the relevant lipoxygenases, thereby skewing the balance towards a pro-resolving lipid mediator profile (129,130).…”

Network- and Enrichment-based Inference of Phenotypes and Targets from large-scale Disease Maps

“…Elements of these maps are linked to public databases and organized into different layers that aid in the visualization and exploration of disease maps. Figure 2 gives an example of a submap from the "Atlas of Inflammation Resolution" (AIR) (Serhan et al, 2020). (AIR).…”