Recently, the new interdisciplinary studies of the tissue engineering are progressing remarkably. These technologies are expected as a breakthrough to overcome the defects and the disadvantages of artificial organs and organ transplantations.
The strategy of the tissue engineering is divided to two groups. One is the in vitro method, and the other is in vivo method.
In the in vitro method, the living cells are picked out and cultured to make some tissues and organs. After that, the tissue or organs are implanted into patient's body.
In the in vivo method, the extracellural matrix which cells can use to make their own environment is settled in the internal body. At that time the stem cells, the precursor cells, and the DDS of cell growth factors to acceralate the growth speed are administrated into the artificial extracellural matrix. Regeneration of almost all of the tissues and organs have already been studied and some of them are tried to apply in clinical patients.
Applying this new technology, the medical therapy will be able to progress and change the thought of the medical therapeutology.

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Generation of prostaglandins (PGs), which are involved in a wide variety of pathophysiological processes, is regulated by three sequential enzymatic reactions. This pathway is initiated by the release of arachidonic acid (AA) by phospholipase A₂s (PLA₂s), followed by its conversion to PGH₂ by cyclooxygenases (COXs) and then to various biologically active PGs by terminal PG synthases (tPGSs) . PLA2 comprises a growing family of enzymes, among which cytosolic PLA₂ (cPLA₂) and several secretory PLA₂s (sPLA₂s) play a crucial role in the release of AA that is supplied to downstream COXs. Activation of cPLA₂ is regulated primarily by perinuclear translocation in response to increased cytoplasmic Ca²⁺ levels and by dual phosphorylation that is under control of the MAP kinase pathway. sPLA₂-mediated eicosanoid generation occurs by two distinct (heparan sulfate- or lipid interface dependent) mechanisms. The two COX isozymes, constitutive COX-1 and inducible COX-2, are functionally segregated in different phases of cell activation. COX-1 mediates the immediate PG generation, in which high levels of AA are released in a short time, whereas COX-2 is a prerequisite for the delayed PG generation, in which low levels of AA are gradually supplied. Furthermore, these COXs are differently coupled with tPGSs, which display unique tissue and subcellular distribution. Identification of two PGE₂ synthases (PGESs) reveals that the constitutive, cytosolic PGES is functionally linked with only COX-1 and the inducible, perinuclear membrane-bound PGES favors COX-2 over COX-1. Overall, our results suggest that the amounts of AA released by cPLA₂ or sPLA₂ and subcellular localization of COXs and tPGSs crucially affect the functional coupling among the biosynthetic enzymes in the cascade.

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Leukocyte adhesion and trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. A newly identified CX₃C-chemokine, fractalkine, expressed on activated endothelial cells, plays an important role in leukocyte adhesion and migration. We found that THP-1 cells, expressing mRNA for fractalkine receptor, CX₃CR 1 efficiently adhered to the membrane bound form of fractalkine expressed on ECV 304 cells or TNF-α-activated HUVECs. Soluble-fractalkine also enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose dependent manner.
However, soluble fractalkine induced little chemotaxis in THP-1 cells in comparison to MCP -1 which induced a strong chemotactic response. Moreover, the membrane form of fractalkine expressed on ECV 304 cells reduced MCP-1-mediated chemotaxis of THP-1 cells. Furthermore, soluble fractalkine enhanced NK cell cytolytic activity against K 562 target cells by enhancing granular exocytosis. Transfection of fractalkine cDNA into ECV 304 cells or HUVECs resulted in increased susceptibility to NK cell-mediated cytolysis compared to control transfection. Together, these results indicate that fractalkine plays an important role not only in the binding of monocytes and NK cells to endothelial cells by enhancing integrin avidity, but also in NK cell-mediated endothelium damage, which may result in vascular injury.

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We studied the role of Jak 2 and Stat 5 in antigen-induced eosinophil recruitment into the airways of sensitized mice. The in vivo administration of a Jak 2 inhibitor AG-490 prevented antigen induced eosinophil recruitment into the airways of sensitized mice in a dose-dependent manner, whereas the administration of AG-490 did not affect antigen induced IL-5 production in the airways. On the other hand, both antigen induced IL -5 production and antigen induced airway eosinophilia was diminished in Stat 5 a-deficient (Stat 5 a^-/-) mice and Stat 5 b-deficient (Stat 5 b^-/-) mice. In addition, eosinophilopoiesis induced by the administration of recombinant IL-5 was diminished in Stat 5 a^-/- mice and Stat 5 b^-/- mice. Interestingly, antigen-induced Th 2 cell differentiation was decreased but antigen-induced Th 1 cell differentiation was increased in Stat 5 a^-/- mice. Together, these results indicate that Jak 2 and Stat 5 activation are essential for the induction of IL-5-dependent, antigen-induced eosinophil recruitment into the airways and that the defects in antigen induced eosinophil recruitment in Stat 5 a^-/- mice and Stat 5 b^-/- mice result from both impaired IL -5 production in the airways and diminished IL -5 responsiveness of eosinophils.

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Objects : To investigate the involvement of thrombin in brain injury, we assessed the effects of argatroban, a specific antithrombin agent, on accumulation of inflammatory cells. We especially focused on the number of ICAM-1 positive vessels and Mac-1 positive cells along the injured brain of rats.
Methods : Gelatins soaked with argatroban or saline were placed in the cavities of artificial brain defect for assessing the grade of inflammatory cells infiltrating, ICAM-1 positive vessels and Mac-1 positive cells were demonstrated by using immunohisto-chemical (IHC) stain. The number of ICAM-1 positive vessels and Mac-1 positive cells stain were compared between argatroban treated and saline (control) groups.
Results : Argatroban suppressed the expression of ICAM-1 on the endothelial cells and also suppressed the infiltration of Mac-1 positive cells along the edge of brain defect.
Conclusion : Argatroban, an antithrombin agent, minimize the secondary brain damage through suppressing both the infiltration of Mac-1 positive cells and expression of ICAM-1 positive vessels.

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Peroxisome proliferator-activated receptor γ (PPARγ) is transcription factors belong to the nuclear receptor gene family and binds to specific response elements termed PPRE, thus regulating the expression of target genes. PPARγ triggers adipocyte differentiation in adipose tissue and inhibits the cytokine production in macrophage. We analyzed the expression of PPARγ in human synovial tissues of patient with rheumatoid arthritis (RA) or osteoarthritis (OA) . PPARγ mRNA strongly expressed in synovial tissues with active RA synovitis more than that of OA. Immunohistological analysis demonstrated PPARγ localized in nuclear area of synovial lining macrophages and vascular endothelial cells in RA synovial tissues. PPARγ expression correlated with the rate of macrophage infiltration and hypervas-cularization in synovial tissues. We measured the expression of PPARγ mRNA in rat arthritic synovial tissues. PT-PCR analysis demonstrated the strong expression of PPARy in rat arthritic joints.
PPARγ ligand, antidiabetic thiazolidinediones (troglitazone) inhibited the synovitis of adjuvant arthritis. These data suggest PPARγ ligands may have therapeutic application in inflammatory arthritis, such as RA.

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To evaluate the effects of ultraviolet-B (UV-B) light for the immune systems, we examined whether UV-B affect to macrophage (Mφ) functions or not. In this study, as an indicator for activation of macrophages induced from UV-B light irradiated mouse, we investigated two Mφ products, radical NO (NO₂^-), and TNFα.
NO₂^- produced by stimulation of lipopolysaccaride (LPS) from macrophage was extensively inhibitted by UV-B irradiation to mice from where Mφ were collected. The inhibition did not depend on the LPS concentration, but it was apparently inhibitted even at high amounts of LPS as well as at low dose one. When TNFα was determined as indicator of activity, the degree of inhibition was various. In an exceptional case, although NO₂^- was extensively inhibited but the inhibition of TNFα was moderate.

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