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Figure 3. Immunomodulatory effects of a synthetic glucocorticoid Dex on microglia. A: effects of 10 agents on NO release by rat primary microglia (A-a) and rat primary cortical neuron-microglia coculture (A-b) incubated for 48 h with LPS. Nitrite levels in conditioned media were determined. Dex suppressed NO release most effectively. *P < 0.05, **P < 0.01, ***P < 0.001, respectively vs. LPS. B: effects of LPS and the agents on LPS-treated neuron-microglia cocultures. B-a: representative immunoblots showing the contents of MAP2 and iNOS proteins in the cocultures. (-LPS) denotes an absence of LPS; B-b: statistical comparison of suppressive effects on LPS-induced iNOS expression; B-c: neuroprotective effects of the 10 agents on the LPS-treated coculture. Strong iNOS expression was correlated with loss of MAP2-immunoreactivity. Only Dex protected neurons significantly from microglial neurotoxicity. Data from four independent cultures are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, respectively, vs. LPS. C: microglia were incubated with an indicated agent for 16 h in the absence of LPS. Only Dex increased expression of mRNAs encoding IGF-1 and HGF significantly while suppressing expression of IL-1β and TNFα mRNAs. n = 4, *P < 0.05, **P < 0.01, ***P < 0.001, respectively, vs. control. D: dose-dependent ameliorative effects of Dex on a rat 6-OHDA-induced PD model. D-a: representative immunoblots showing dose-dependent effects of Dex on the content of TH, a DA neuron marker; D-b: statistical analyses of the dose-dependent effects of Dex. A dose 0.003 µg/kg weight of Dex significantly prevented the reduction in TH immunoreactivity. Data from four rats for each dose were expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, respectively vs. 6-OHDA/Dex 0. The data are from unpublished ones by Wada et al. (unpublished data). Dex: dexamethasone; Ald: aldosterone; Imi: imipramine; Flu: fluvoxamine; Ind: indomethacin; Ibu: ibuprofen; Ter: terbutaline; Iso: isoproterenol; Min: minocycline; Tro: troglitazone; LPS: lipopolysaccharide; TH: tyrosine hydroxylase; DA: dopaminergic; PD: Parkinson’s disease; HGF: hepatocyte growth factor; IGF-1: insulin-like growth factor 1; 6-OHDA: 6-hydorxydopamine; iNOS: inducible nitric oxide synthase