Increased serum GP88 (Progranulin) concentrations in rheumatoid arthritis.

GP88 (Progranulin; PGRN) is a secreted glycosylated protein with important functions in several processes, including immune response and cancer growth. Recent reports have shown that PGRN is a therapeutic target for rheumatoid arthritis (RA) because of its capability to bind with tumor necrosis factor receptor (TNFR). However, the serum PGRN level in RA patients has not been investigated. We used enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of PGRN in 417 healthy subjects, 56 patients with RA and 31 patients with osteoarthritis (OA). In RA patients, we also measured the serum TNF-α and sTNFR concentration. Immunohistochemical staining of PGRN was performed using synovectomy tissue of RA patients. The serum PGRN normal range was established as 40.1 ± 8.7 ng/ml. PGRN levels were not influenced by sex or age. A significant increase in serum PGRN levels was observed in RA (50.2 ± 11.1 ng/ml) and OA (45.4 ± 6.6 ng/ml) groups compared to those in age-matched healthy controls (40.4 ± 9.9 ng/ml) (p<0.05, Tukey). Further, PGRN levels in the synovial fluid of RA patients (68.4 ± 3.4 ng/ml) were found to be significantly higher than those in OA patients (35.9 ± 16.8 ng/ml). Immunohistochemical staining of PGRN revealed that the highest positive signal was detected in macrophages. Circulating PGRN in RA patients was weakly associated with TNF-α and sTNFR 2 concentration. Furthermore, PGRN/TNF-α ratio was correlated the stage of the disease in RA patients. The concentrations of serum PGRN in RA were found to be significantly higher than those in age-matched healthy controls, although it remains to be clarified how blood PGRN is related to the pathogenesis of RA. Our results showed that the serum PGRN may be a useful approach to monitor the disease activity in RA patients.

Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.

Indoleamine 2,3-dioxygenase (IDO) 1, that catalyzes the first and rate-limiting step in the degradation of L-tryptophan, has an important immunomodulatory function. The activity of IDO1 increases in various inflammatory diseases, including tumors, autoimmune diseases, and different kinds of inflammation. We evaluated the suppressive effect of plant extracts or phytochemicals on IDO1 induction and activity; sixteen kinds of plants extracts and fourteen kinds of phytochemicals were examined. As a result, the methanol extracts of Myoga flower buds, which are traditional Japanese foods, and labdane-type diterpene galanal derived from Myoga flowers significantly suppressed IDO1 activity. The Lineweaver-Burk plot analysis indicated that galanal is a competitive inhibitor. Galanal attenuated L-kynurenine formation with an IC50 value of 7.7 µM in the assay system using recombinant human IDO1, and an IC50 value of 45 nM in the cell-based assay. Further, mechanistic analysis revealed that galanal interfered with the transcriptional function of the nuclear factor-κB and the interferon-γ signaling pathway. These effects of galanal are important for immune response. Because the inhibitory effect of galanal on IDO1 activity was stronger than that of 1-methyl tryptophan, a tryptophan analog, galanal may have great potential as the novel drug for various immune-related diseases.

[Significance and utilization of "RECHS" (Resource Center for Health Science) focusing on the importance of human bio-resources].

The Resource Center for Health Science (RECHS) has initiated a project based on the development and utilization of Bio-Resources/Database (BR/DB), comprising personal health records(PHR), such as health/medical records of the health of individuals, physically consolidated with bio-resources, e.g. serum, urine etc. taken from the same individuals. This is characterized as analytical alterations of BR/DB annually collected from healthy individuals, targeting 100,000, but not as data dependent on the number of unhealthy individuals so far investigated. The purpose is to establish a primary defense for the improvement of QOL by applying BR/DB to analysis by epidemiology and clinical chemistry. Furthermore, it also contributes to the construction of a PHR system planned as a national project. The RECHS coordinating activities are fully dependent on as many general hospitals as possible on the basis of regional medical services, and academia groups capable of analyzing BR/DB.