Biology subjects

Pedersen, M. E.

Publications and source records attributed to Pedersen, M. E..

4 recordsLinked to original sources

bioRxiv2025

Herring roe oil exerts anti-psoriatic and immunomodulatory effects on the IL-17/23 signaling axis in macrophages, T-cells and a keratinocyte and fibroblast co-culture

BackgroundSeveral systemic treatment options are available for moderate to severe psoriasis, while low-risk oral treatments for milder forms are limited. Herring roe oil (HRO) has previously shown beneficial effects on the clinical presentation of psoriasis, however, cell-specific effects remained unknown. ObjectiveThis study aimed to elucidate cellular effects of HRO and whether signaling pathways in skin and immune cells relevant to the pathophysiology of psoriasis are affected by HRO. MethodsWe used cell-culture models of human primary macrophages and T-cells, the keratinocyte cell line HaCat and human primary fibroblasts to represent important site-specific pathological aspects of psoriasis in the skin and immune system. The cells were supplemented with HRO emulsions and cellular signaling was analyzed on protein and mRNA level. Skin cell proliferation was analyzed in real-time by a Live-Cell Analysis System. ConclusionWe here present results which suggest that HRO exerts effects on different cell types on major psoriasis-driving aspects, reducing the secretion of IL-23 and IL-17 from macrophages and T-cells, respectively, as well as interfering with IL-17-induced signaling and proliferation of keratinocytes in co-culture with fibroblasts. Clinicaltrials.gov (or equivalent) listing (if applicable): not applicable Key PointsO_LIWhy was the study undertaken? To elucidate cellular targets for the anti-psoriatic effects of HRO. C_LIO_LIWhat does this study add? This study adds an understanding of cell specific effects of HRO that support a clinically beneficial action on psoriasis. C_LIO_LIWhat are the implications of this study for disease understanding and/or clinical care? This study supports the use of HRO as treatment option for mild-to-moderate psoriasis. C_LI

immunology↗

bioRxiv2025

Phospholipid esters from herring roe promotes SPM biosynthesis in human monocyte-derived macrophages and a keratinocyte/fibroblast co-culture with implications for the treatment of psoriasis

Psoriasis is a chronic immune-mediated inflammatory disease (IMID) affecting the skin presenting with both local and systemic inflammation as part of its pathophysiology. An oil rich in phospholipids extracted from herring roe has been shown to have immunomodulatory properties and to improve clinical symptoms and impact inflammatory cytokine pathways in psoriasis in a clinical trial. The lipidic nature of herring roe oil (HRO) and its high content of polyunsaturated fatty acids suggests involvement of lipid mediator pathways for the observed alleviation of psoriatic inflammation. Of particular interest is the super-family of lipid mediators termed specialized pro-resolving mediators (SPMs), due to their involvement in resolution of inflammation and subsequent return to homeostasis. We therefore explored the influence of HRO and its phospholipids on lipid mediator and SPM biosynthesis in IFN-{gamma} and LPS-stimulated human monocyte-derived macrophages and an IL-17A-stimulated keratinocyte/fibroblast co-culture. Lipid mediators including SPMs were quantified from cell supernatants using a validated LC-MS/MS protocol. In these experiments we observed broad SPM biosynthesis with dominant upregulation of RvE2 and RvE3 in both cell systems and upregulation of DHA-derived SPMs such as RvD2 and PDX. Observations of PCTR2 in macrophage cell supernatants also indicate activation of reparative pathways upon treatment with HRO. In conclusion, we observed promotion of SPM biosynthesis associated with a shift towards a protective and possibly reparative macrophage phenotype as well as promotion of biosynthesis of pro-resolving lipid mediators in a skin cell co-culture, thus demonstrating a possible mechanism for resolution of inflammation in the skin niche using HRO.

biochemistry↗

bioRxiv2020

Atypical TGF-beta Signaling Controls Neuronal Guidance in Caenorhabditis elegans

Coordinated expression of cell adhesion and signaling molecules is crucial for brain development. Here, we report that the Caenorhabditis elegans transforming growth factor-beta (TGF-{beta}) type I receptor SMA-6 (small-6) acts independently of its cognate TGF-{beta} type II receptor DAF-4 (dauer formation-defective-4) to control neuronal guidance. SMA-6 directs neuronal development from the epidermis through interactions with three, orphan, TGF-{beta} ligands. Intracellular signaling downstream of SMA-6 limits expression of NLR-1, an essential Neurexin-like cell adhesion receptor, to enable neuronal guidance. Together, our data identify an atypical TGF-{beta}-mediated regulatory mechanism to ensure correct development of the nervous system.

developmental biology↗

bioRxiv2020

Syndecan-4-/- mice have smaller muscle fibers, increased Akt/mTOR/S6K1 and Notch/HES-1 pathways, and alterations in extracellular matrix components

BackgroundExtracellular matrix (ECM) remodeling is essential for skeletal muscle development and adaption in response to environmental cues such as exercise and injury. The cell surface proteoglycan syndecan-4 has been reported to be essential for muscle differentiation, but few molecular mechanisms are known. Syndecan-4-/- mice are unable to regenerate damaged muscle, and display deficient satellite cell activation, proliferation, and differentiation. A reduced myofiber basal lamina has also been reported in syndecan-4-/- muscle, indicating possible defects in ECM production. To get a better understanding of the underlying molecular mechanisms, we have here investigated the effects of syndecan-4 genetic ablation on molecules involved in ECM remodeling and muscle growth, both under steady state conditions and in response to exercise. MethodsTibialis anterior (TA) muscles from sedentary and exercised syndecan-4-/- and WT mice were analyzed by immunohistochemistry, real-time PCR and western blotting. ResultsCompared to WT, we found that syndecan-4-/- mice had reduced body weight, reduced muscle weight, muscle fibers with a smaller cross-sectional area, and reduced expression of myogenic regulatory transcription factors. Sedentary syndecan-4-/- had also increased mRNA levels of syndecan-2, decorin, collagens, fibromodulin, biglycan, and LOX. Some of these latter ECM components were reduced at protein level, suggesting them to be more susceptible to degradation or less efficiently translated when syndecan-4 is absent. At the protein level, TRPC7 was reduced, whereas activation of the Akt/mTOR/S6K1 and Notch/HES-1 pathways were increased. Finally, although exercise induced upregulation of several of these components in WT, a further upregulation of these molecules was not observed in exercised syndecan-4-/- mice. ConclusionsAltogether our data suggest an important role of syndecan-4 in muscle development.

cell biology↗