2-Methoxyestradiol-3,17-O,O-bis-sulfamate inhibits store-operated Ca entry in T lymphocytes and prevents experimental autoimmune encephalomyelitis.

Ca signaling is one of the essential signaling systems for T lymphocyte activation, the latter being an essential step in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Store-operated Ca entry (SOCE) ensures long lasting Ca signaling and is of utmost importance for major downstream T lymphocyte activation steps, e.g.

Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like Mouse Model Evoke Complement Component C5a Independent of C3.

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD).

2-Methoxyestradiol and its derivatives inhibit store-operated Ca entry in T cells: Identification of a new and potent inhibitor.

T cell activation starts with formation of second messengers that release Ca from the endoplasmic reticulum (ER) and thereby activate store-operated Ca entry (SOCE), one of the essential signals for T cell activation. Recently, the steroidal 2-methoxyestradiol was shown to inhibit nuclear translocation of the nuclear factor of activated T cells (NFAT). We therefore investigated 2-methoxyestradiol for inhibition of Ca entry in T cells, screened a library of 2-methoxyestradiol analogues, and characterized the derivative 2-ethyl-3-sulfamoyloxy-17β-cyanomethylestra-1,3,5(10)-triene (STX564) as a novel, potent and specific SOCE inhibitor.

Macrophage to myofibroblast transition contributes to subretinal fibrosis secondary to neovascular age-related macular degeneration.

Background: Macular fibrosis causes irreparable vision loss in neovascular age-related macular degeneration (nAMD) even with anti-vascular endothelial growth factor (VEGF) therapy. Inflammation is known to play an important role in macular fibrosis although the underlying mechanism remains poorly defined. The aim of this study was to understand how infiltrating macrophages and complement proteins may contribute to macular fibrosis.

Cytokine Signaling Protein 3 Deficiency in Myeloid Cells Promotes Retinal Degeneration and Angiogenesis through Arginase-1 Up-Regulation in Experimental Autoimmune Uveoretinitis.

The suppressor of cytokine signaling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysMSOCS3). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysMSOCS3 mice compared with that in wild-type (WT) mice.