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Apolipoproteins in the cerebrospinal fluid (CSF) play important roles in lipid metabolism in the central nervous system. Although it has been demonstrated that apo E is synthesized in the neuron, the synthesis of apo A-I has only been determined in fish and chicken. It was demonstrated that apo A-I concentrations in the CSF were increased in poliovirus-infected macaques, however, the origin of the CSF apo A-I was not determined. The present immunohistochemical study provided evidence that apo A-I was localized within the nerve cell body of the rat spinal cord. In situ hybridization also showed that apo A-I mRNA was predominantly expressed in the neurons. As a further experiment, we compared apo A-I levels in the spinal cord from control rats and rats with experimental allergic encephalomyelitis (EAE), which was induced by sensitization with myelin basic protein. Although no significant changes in serum apo A-I levels were observed, apo A-I levels in the spinal cord were significantly elevated in EAE rats. Furthermore, apo A-I in the spinal cord of rats with EAE was not seen in the nerve cell body, but at the interstitium, particularly in lesions where inflammation had occurred. The current study clearly demonstrated that apo A-I is synthesized in the neurons of the rat spinal cord and the synthesis was suppressed in EAE rats.

L-Tryptophan degradation by indoleamine 2,3-dioxygenase (IDO) induction and reactive nitrogen intermediates produced by inducible nitric oxide synthase (iNOS) induction are important factors for IFN-gamma-induced anti-toxoplasma activities. In the present study, the effects of acute Toxoplasma gondii (T. gondii) infection on IDO and iNOS were investigated using wild-type (WT) and IFN-gamma gene-deficient (IFN-gamma KO) mice. In the WT C57BL/6J mice, enzyme activities and mRNA levels of IDO in both lung and brain were markedly increased, and lung L-tryptophan concentrations were dramatically decreased following infection. In contrast, these metabolic changes did not occur in infected IFN-gamma KO mice. The level of iNOS induction in the infected IFN-gamma KO mice was high in lung and low in brain compared to that in infected WT mice. The extent of increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) in lung and brain induced by infection was significantly enhanced in the IFN-gamma KO mice compared to that in WT mice. Treatment with N-nitro-L-arginine methyl ester, an iNOS inhibitor, increased the levels of SAG2 mRNA in brain, but not in lung following infection. This in vivo study provides evidence that L-tryptophan depletion caused by T. gondii is directly mediated by IFN-gamma in the lung, where iNOS is not induced by IFN-gamma. This study suggests that there is an anti-toxoplasma mechanism of cross-regulation between iNOS and IDO and that the expression of main anti-parasite effector mechanisms of iNOS and/or IDO may vary among tissues.

We determined serum metalloproteinase-3(MMP-3) and inflammatory cytokine(IL-6, IL-8) levels in patients with rheumatoid arthritis(RA). Sera were obtained from 307 healthy subjects(female 140, male 167), 54 RA patients, and 17 osteoarthritis (OA). The MMP-3 concentrations in healthy female and male were 43.3 +/- 15.3 ng/ml and 90.7 +/- 26.0 ng/ml, respectively. The serum MMP-3 levels in male were significantly higher than those in female (p0.0001). MMP-3 levels in RA patients(259.1 +/- 34.2 ng/ml) were significantly higher than OA(43.6 +/- 6.1 ng/ml) or healthy controls. There was a significant correlation between MMP-3 and CRP(r = 0.586), IL-6(r = 0.345) levels in serum. In contrast, no significant correlation was observed between MMP-3 and IL-8(r = 0.19), or CA-RF(r = 0.052) levels. However, there were some cases with high MMP-3 levels in CA-RF-negative patients definitely diagnosed as RA. These findings suggest that MMP-3 determination is useful for the early diagnosis and the follow-up during the treatment for RA patients.

L-Tryptophan degradation by indoleamine 2,3-dioxygenase (IDO) induction and reactive nitrogen intermediates produced by inducible nitric oxide synthase (iNOS) induction are important factors for IFN-gamma-induced anti-toxoplasma activities. In the present study, the effects of acute Toxoplasma gondii (T. gondii) infection on IDO and iNOS were investigated using wild-type (WT) and IFN-gamma gene-deficient (IFN-gamma KO) mice. In the WT C57BL/6J mice, enzyme activities and mRNA levels of IDO in both lung and brain were markedly increased, and lung L-tryptophan concentrations were dramatically decreased following infection. In contrast, these metabolic changes did not occur in infected IFN-gamma KO mice. The level of iNOS induction in the infected IFN-gamma KO mice was high in lung and low in brain compared to that in infected WT mice. The extent of increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) in lung and brain induced by infection was significantly enhanced in the IFN-gamma KO mice compared to that in WT mice. Treatment with N-nitro-L-arginine methyl ester, an iNOS inhibitor, increased the levels of SAG2 mRNA in brain, but not in lung following infection. This in vivo study provides evidence that L-tryptophan depletion caused by T. gondii is directly mediated by IFN-gamma in the lung, where iNOS is not induced by IFN-gamma. This study suggests that there is an anti-toxoplasma mechanism of cross-regulation between iNOS and IDO and that the expression of main anti-parasite effector mechanisms of iNOS and/or IDO may vary among tissues.