Monocyte chemotactic protein-1 gene expression and translation in formed granulomatous calcified tissue in vivo

Monocyte chemotactic protein-1 (MCP-1) and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory propert ies. However, the exact role, function, and implication in inflammatory dis eases remain to be determined. Here we report that subcutaneous injections (0.2 mi) of a saturated water solution (1:40) of potassium permanganate cry stals induces the generation of granuloma tissue at the site of injection i n the rat, and reaches its peak of formation after 1 week. The size and wei ght of the granulomas were increased by i.p. lipo polysaccharide (LPS) (6 m u g/200 mu l) and inhibited by intraperitoneal (i.p.) dexamethasone (Dxs) 3 00 mu g/200 mu l) treatments in rats, injected 18 hours before sacrifice. M oreover, steady-state levels of MCP-I mRNA in the granuloma tissue (control ), were strongly generated. Rats treated i.p. with LPS produced an increase of MCP-1 mRNA in the granuloma tissue compared with controls (i.p. PBS-tre ated) whereas in animals treated with Dxs, there was a decrease in (P < 0.0 5) in formation of mRNA protein. When the granuloma tissues were homogenize d the generation of MCP-I was found in the supernatants. The level of MCP-1 was higher (P < 0.05) in the LPS-treated animals and lower (P < 0.05) in t he Dxs group compared with the controls (treated with PBS). Similar results were obtained in the serum and in minced granuloma tissue where samples we re further incubated in vitro with LPS (100 ng/ml) overnight. A Strong incr ease (P < 0.01) in MCP-1 in all samples was detected, but not in the minced granuloma tissue from Dxs-treated animals. Our data demonstrate that calci fied tissue from chronic inflammation induced by KMnO4 generates MCP-1 gene expression and translation, an effect increased by LPS and decreased by Dx s.