Formyl Peptide Receptor 2 Activation Ameliorates Dermal Fibrosis and Inflammation in Bleomycin-Induced Scleroderma
Gyu Tae Park,Yang Woo Kwon,Tae Wook Lee,Seong Gyu Kwon,Hyun-Chang Ko,Moon-Bum Kim,Jae Ho Kim +6 more
TLDR
In this paper, the authors investigated the effects of Fpr2 activation in the treatment of scleroderma fibrosis and found that intradermal administration of WKYMVm, a G protein-coupled receptor that modulates inflammation and host defense by regulating the activation of inflammatory cells, such as macrophages.Abstract:
Systemic sclerosis is a profibrotic autoimmune disease mediated by the dysregulation of extracellular matrix synthesis. Formyl peptide receptor 2 (Fpr2) is a G protein-coupled receptor that modulates inflammation and host defense by regulating the activation of inflammatory cells, such as macrophages. However, the role of Fpr2 in the development and therapy of scleroderma is still unclear. The present study was conducted to investigate the effects of Fpr2 activation in the treatment of scleroderma fibrosis. We found that intradermal administration of WKYMVm, an Fpr2-specific agonist, alleviated bleomycin-induced scleroderma fibrosis in mice and decreased dermal thickness in scleroderma skin. WKYMVm-treated scleroderma skin tissues displayed reduced numbers of myofibroblasts expressing α-smooth muscle actin, Vimentin, and phosphorylated SMAD3. WKYMVm treatment attenuated macrophage infiltration in scleroderma skin and reduced the number of M2 macrophages. The therapeutic effects of WKYMVm in scleroderma-associated fibrosis and inflammation were completely abrogated in Fpr2 knockout mice. Moreover, WKYMVm treatment reduced the serum levels of inflammatory cytokines, such as tumor necrosis factor-α, and interferon-γ, in the scleroderma model of wild-type mice but not in Fpr2 knockout mice. These results suggest that WKYMVm-induced activation of Fpr2 leads to alleviation of fibrosis by stimulating immune resolution in systemic sclerosis.read more
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Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation
TL;DR: The activation of NRF2 by docosahexanoic acid, eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA are discussed.
Journal ArticleDOI
Predicting Resolvin D1 Pharmacokinetics in Humans with Physiologically Based Pharmacokinetic Modeling
Venkata K. Yellepeddi,Kaustubh Parashar,Spencer M. Dean,Kevin M. Watt,Jonathan E. Constance,Olga J. Baker +5 more
TL;DR: A physiologically‐based pharmacokinetic (PBPK) model of RvD1 in mice and optimized the model using plasma and salivary gland pharmacokinetics studies performed in NOD/ShiLtJ mice with SS‐like features will be useful for the clinical trial design and translation of R vD1 as an effective treatment strategy for SS.
Journal ArticleDOI
WKYMVm ameliorates acute lung injury via neutrophil antimicrobial peptide derived STAT1/IRF1 pathway
TL;DR: The data suggest therapeutic potential of WKYMVm, via FPR2-dependent regulation of STAT1/IRF1, in ALI, in mice.
Journal ArticleDOI
MAP kinases in regulation of NOX activity stimulated through two types of formyl peptide receptors in murine bone marrow granulocytes
TL;DR: In this paper, the role of MAPKs in the activation of NADPH oxidase through FPR1 and FPR2 was investigated and it was shown that p38 MAPK and ERK were involved in fpr1 induced ROS generation only.
Journal ArticleDOI
A Ganoderma-Derived Compound Exerts Inhibitory Effect Through Formyl Peptide Receptor 2.
Huirong Wang,Huirong Wang,Xingrong Peng,Yunjun Ge,Shuo Zhang,Zhenyi Wang,Yu Fan,Wei Huang,Ming-Hua Qiu,Richard D. Ye,Richard D. Ye +10 more
TL;DR: Results identified for the first time that a Ganoderma-derived component with inhibitory effects that acts through a G protein-coupled receptor FPR2, resulting in reduced superoxide production and compromised cell chemotaxis.
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