Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc. In this study, we observed a novel effect of S1P5 on the inflammatory processes during low-dose bleomycin (BLM)-induced fibrogenesis in murine skin. By comparing 2-week-treated skin areas of wild-type (WT) and S1P5-deficient mice, we found that S1P5 is important for the transcriptional upregulation of the Th2 characteristic transcription factor under treatment-induced inflammatory conditions, while (Th1) and (Treg) mRNA expression was regulated independently of S1P5. Additionally, treatment caused a regulation of and mRNA as well as a regulation of long-chain ceramide profiles, which both differ significantly between the genotypes. Despite S1P5-dependent differences regarding inflammatory processes, similar macroscopic evidence of fibrosis was detected in the skin histology of WT and S1P5-deficient mice after 4 weeks of subcutaneous BLM treatment. However, at the earlier 2-week point in time, the mRNA data of and indicate a pro-fibrotic S1P5 contribution in the applied SSc mouse model. In conclusion, we propose that S1P5 plays a role as a novel modulator during the early phase of BLM-caused fibrogenesis in murine skin. An immediate relationship between dermal S1P5 expression and fibrotic processes leading to skin alterations, such as formative for SSc pathogenesis, is indicated but should be studied more profound in further investigations. Therefore, this study is an initial step in understanding the role of S1P5-mediated effects during early stages of fibrogenesis, which may encourage the ongoing search for new therapeutic options for SSc patients.
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http://dx.doi.org/10.3389/fimmu.2017.01242 | DOI Listing |
Arch Dermatol Res
January 2025
Faculty of Pharmacy, Iryo Sosei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima, 970-8551, Japan.
Atopic dermatitis (AD), also known as eczema, is a chronic or relapsing inflammatory skin disease characterized by repeated exacerbations and remissions. Here, we investigated the effects of squid phospholipids (PLs) extracted from Todarodes pacificus on AD. The composition of squid PLs was analyzed using thin-layer chromatography and high-performance liquid chromatography, and the effects of PLs on AD were investigated using a rat paw edema model and an AD-like mouse model (NC/Nga mice).
View Article and Find Full Text PDFJ Mol Histol
January 2025
Department of Structural and Functional Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
This study investigated tempol action on genes and miRNAs related to NFκB pathway in androgen dependent or independent cell lines and in TRAMP model in the early and late-stages of cancer progression. A bioinformatic search was conducted to select the miRNAs to be measured based on the genes of interest from NFκB pathway. The miR-let-7c-5p, miR-26a-5p and miR-155-5p and five target genes (BCL2, BCL2L1, RELA, TNF, PTGS2) were chosen for RT-PCR and gene enrichment analyses.
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Model System for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany.
Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)).
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
Bristol Centre for Antimicrobial Research & Evaluation (BCARE), Infection Sciences, Southmead Hospital, Westbury-on-Trym, Bristol, UK.
Background: NOSO-5O2 is the first clinical candidate of a new antimicrobial class-the odilorhabdins. The pharmacodynamics of NOSO-502 were studied in vitro and in vivo to establish the pharmacodynamic index (PDI) driver.
Methods: A dilutional pharmacokinetic system was used for in vitro experiments.
J Pathol
January 2025
Department of Clinical Bio-resource Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Spread through air spaces (STAS) is a histological finding of lung tumours where tumour cells exist within the air space of the lung parenchyma beyond the margin of the main tumour. Although STAS is an important prognostic factor, the pathobiology of STAS remains unclear. Here, we investigated the mechanism of STAS by analysing the relationship between STAS and polarity switching in vivo and in vitro.
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