The Authoritative Germanium Sesquioxide Resource

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An anti-inflammatory drug, propagermanium, may target GPI-anchored proteins associated with an MCP-1 receptor, CCR2. J Interferon Cytokine Res. 2001 Jun;21(6):389-98.

Yokochi S, Hashimoto H, Ishiwata Y, Shimokawa H, Haino M, Terashima Y, Matsushima K.

Central Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Hokusei-cho, Inabe-gun, Mie 511-0406, Japan.

Monocyte chemoattractant protein-1 (MCP-1) promotes the migration and activation of monocytes and plays a pivotal role in the development of chronic inflammation. Propagermanium (3-oxygermylpropionic acid polymer) has been used as a therapeutic agent against chronic hepatitis B in Japan. We report here that propagermanium specifically inhibits in vitro chemotactic migration of monocytes by MCP-1. Propagermanium did not inhibit binding of MCP-1 to a human monocytic cell line, THP-1 cells, or affect intracellular Ca(2+) mobilization or the cAMP concentration in MCP-1-treated THP-1 cells. The effect of propagermanium seems to require glycosylphosphatidylinositol (GPI)-anchored proteins, as cleavage of GPI anchors by phosphatidylinositol-phospholipase C (PI-PLC) eliminated the inhibitory activity of propagermanium. Anti-GPI-anchored protein antibodies, such as anti-CD55 and anti-CD59, reduced staining of C-C chemokine receptor 2 (CCR2) with an anti-CCR2 antibody against the N-terminus of CCR2 in a flow cytometric analysis, and these antibodies also selectively inhibited MCP-1-induced migration of THP-1 cells. Furthermore, under fluorescence microscopy, GPI-anchored proteins colocalized with CCR2 on THP-1 cells. These results suggest that propagermanium may target GPI-anchored proteins that are closely associated with CCR2 to selectively inhibit the MCP-1-induced chemotaxis, thus providing a mechanistic basis for the anti-inflammatory effects of the drug.

Anti-inflammatory, Pain Management
Anti-inflammatory effect of germanium-concentrated yeast against paw oedema is related to the inhibition of arachidonic acid release and prostaglandin E production in RBL 2H3 cells.  Auton Autacoid Pharmacol. 2005 Oct;25(4):129-34.

Lee JH, Kim KW, Yoon MY, Lee JY, Kim CJ, Sim SS.

Department of Pathophysiology, College of Pharmacy, Chung-Ang University, 221 Huksuk-dong, Dongjak-gu, Seoul 156-756, South Korea.

To investigate anti-inflammatory activity of organic germanium, we measured the effect of germanium-concentrated yeast on arachidonic acid release, prostaglandin E(2) (PGE(2)) production, histamine release, and intracellular H(2)O(2) or hydroperoxide generation in RBL 2H3 cells, and carrageenan-induced paw oedema in rats. 2 Germanium-concentrated yeast dose-dependently inhibited carrageenan-induced paw oedema, suggesting that germanium-concentrated yeast has anti-inflammatory activity in acute inflammation. 3 Germanium-concentrated yeast significantly inhibited melittin-induced arachidonic acid release and PGE(2) production in RBL 2H3 cells. 4 Germanium-concentrated yeast did not affect melittin-induced histamine release and silica-induced intracellular H(2)O(2) or hydroperoxide generation in RBL 2H3 cells. 5 These results suggest that anti-inflammatory activity of germanium-concentrated yeast appears partly to be related to the inhibition of arachidonic acid release and PGE(2) production in RBL 2H3 cells. PMID: 16176443 [PubMed - indexed for MEDLINE]

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