Neolignan Derivatives from the Flower of Magnolia biondii Pamp. and their Effects on IL-2 expression in T-cells

The isolation of the MeOH extract from the flower bud of Magnolia biondii Pamp. using various column chromatographies and HPLC led to eleven neoglignan derivatives (1 - 11). Their structures were mainly determined by 1D and 2D NMR spectral data analysis and physiological methods. The isolated compounds (1 - 11) were tested for anti-allergic effects using IL-2 inhibitory assay in Jurkat T cells.

Swiprosin-1 Expression Is Up-Regulated through Protein Kinase C-theta and NF-kappaB Pathway in T Cells

Swiprosin-1 exhibits the highest expression in CD8+ T cells and immature B cells and has been proposed to play a role in lymphocyte biology through actin remodeling. However, regulation of swiprosin-1 gene expression is poorly understood. Here we report that swiprosin-1 is up-regulated in T cells by PKC pathway. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that PKC-theta is involved in the expression of swiprosin-1 in the human T cells. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. Interestingly, swiprosin-1 expression is only reduced by treatment with NF-kappaB inhibitors but not by NF-AT inhibitor, suggesting that the NF-kappaB pathway is critical for regulation of swiprosin-1 expression. Collectively, these results suggest that swiprosin-1 is a PKC-theta-inducible gene and that it may modulate the late phase of T cell activation after antigen challenge.

Actin Engine in Immunological Synapse

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse.

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function-associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

ICAM-1/LFA-1 interaction contributes to the induction of endothelial cell-cell separation: implication for enhanced leukocyte diapedesis

The basic route and mechanism for diapedesis has not yet to be fully defined. Here we present evidence that "cell-cell separation" between endothelial cells (ECs) may provide a route for leukocyte diapedesis. We unexpectedly found that extensive interaction between peripheral blood leukocytes and ECs that were activated by TNF-alpha induced the opening of EC contacts and, surprisingly, resulted in cell-cell separation. This event was specific to the intercellular adhesion molecules-1 (ICAM-1)/leukocyte function-associated antigen-1 interaction, as demonstrated by the following: (1) ICAM-1 expression correlated with increased EC contraction; and (2) the blocking of ICAM-1 selectively inhibited EC separation. Thus, we suggest that "cell-cell separation" could be a mechanism for diapedesis in situations that may require massive leukocyte infiltration.

Granulocyte Colony Stimulating Factor (G-CSF) Attenuates 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-induced Colitis in Mice

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti-inflammatory way. METHODS: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. RESULTS: Recombinant human G-CSF significantly inhibited LPS-induced TNF-alpha mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-alpha, interleukin-1beta, and intercellular adhesion molecule-1 in TNBS colitis. CONCLUSION: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

Cytoplasmic Domain of Intercellular Adhesion Molecule-1(ICAM-1)is Important for the ICAM-1 Mediated Membrane Projection of Endothelial Cells / 대한해부학회지

Intercellular adhesion molecule-1 (ICAM-1)has been shown to enhance leukocyte adhesion, thereby inducing migration through blood endothelial cells. However, the molecular event during the process of adhesion is largely unknown. To examine the role of ICAM-1 cytoplasmic domain in SDF-1 alpha-induced T lymphocyte migration and adhesion, mutant human ICAM-1 molecules were expressed in COS-7 cell line. COS-7 cells expressing ICAM-1_GFP mutant without alpha-actinin revealed no association with the actin cytoskeleton, while wild-type ICAM-showed clear association with the actin, as observed by confocal microscopy, suggesting that actinin binding motif in the cytoplasmic domain of ICAM-1 is important for the proper localization of ICAM-1 on the cell membrane. However, based on adhesion assay, we found that the cytoplasmic domain of ICAM-1 is not essential for the binding of lymphocytes which were activated by SDF-1alpha. On the other hand, ICAM-1-mediated receptor-ligand clustering event was significantly inhibited in the cells expressing ICAM-1 mutants without alpha-actinin or whole cytoplasmic domain. Taken together, these results suggest that ICAM-1 cytoplasmic domain is not essential for the adhesion but important for the ligand-receptor-mediated membrane projection of endothelial cells before trans-endothelial migration of lymphocytes.

Involvement of Protein Kinase C delta in Iron Chelator-Induced IL-8 Production in Human Intestinal Epithelial Cells / 대한해부학회지

Our previous study demonstrated that a bacterial siderophore, deferoxamine (DFO), could trigger inflammatory signals in human intestinal epithelial cells as a single stimulus, leading to IL-8 production via ERK1/2 and p38 phosphorylation and NF-kappa B-independent mechanism. In the present study, we proved that a novel protein kinase C (PKC)isoform, PKCdelta, is necessary for DFO-induced IL-8 production. Pretreatment of HT-29 cells with rottlerin showed remarkable inhibition of DFO-induced IL-8 production. In contrast, a conventional PKC inhibitor Go6976 did not show significant inhibition of DFO-induced IL-8 production. DFO induced strong phosphorylation of PKCdelta in the epithelial cells. Overexpression of PKCdelta resulted in enhanced PKCdelta phosphorylation, while transfection with dominant-negative PKCdelta vector failed DFO-induced phosphorylation. In addition, transfection of HT-29 cells with siRNA targeting endogenous PKCdelta, which suppressed PKCdelta expression, attenuated DFO-induced IL-8 production. These results demonstrate that PKCdelta plays an important role in regulating iron chelator-induced IL-8 production in human intestinal epithelial cells.

Iron chelator inducesMIP-3alpha/CCL20 in human intestinal epithelial cells: implication for triggeringmucosal adaptive immunity

A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarray-based gene expression profiling revealed that iron chelator also induces macrophage inflammatory protein 3 alpha (MIP-3alpha)/ CC chemokine-ligand 20 (CCL20). As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as recombinant human CCL20 at equivalent concentrations to attract CCR6+ cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human PBMCs and in THP-1 cells, but not in human umbilical vein endothelial cells. Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.

Ulcerative Colitis is Associated with Novel Polymorphisms in the Promoter Region of MIP-3alpha/CCL20 Gene

BACKGROUND: We examined global gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with ulcerative colitis (UC), and tested whether the identified genes with the altered expression might be associated with susceptibility to UC. METHODS: PBMCs from 8 UC and 8 normal healthy (NH) volunteers were collected, and total RNAs were subjected to the human 8.0K cDNA chip for the microarray analysis. Real time-PCR (RT-PCR) was performed to verify the results of microarray. One hundred forty UC patients and 300 NH controls were recruited for single nucleotide polymorphism (SNP) analysis. RESULTS: Twenty-five immune function-related genes with over 2-fold expression were identified. Of these genes, two chemokines, namely, CXCL1 and CCL20, were selected because of their potential importance in the evocation of host innate and adaptive immunity. Four SNPs were identified in the promoter and coding regions of CXCL1, while there was no significant difference between all patients with UC and controls in their polymorphisms, except minor association at g.57A< G (rs2071425, p=0.02). On the other hand, among three novel and one known SNPs identified in the promoter region of CCL20, g.-1,706 G< A (p=0.000000055), g.-1,458 G< A (p=0.0048), and g.-962C< A (p=0.0006) were found to be significantly associated with the susceptibility of UC. CONCLUSION: Altered gene expression in mononuclear cells may contribute to IBD pathogenesis. Although the findings need to be confirmed in other populations with larger numbers of patients, the current results demonstrated that polymorphisms in the promoter region of CCL20 are positively associated with the development of UC.

Effects of Sulphasalazine and Glucocorticoid on the Regulation of CCL20 Gene Expression in the Peripheral Blood Cells of Korean Patients with Ulcerative Colitis / 대한해부학회지

Discovery of Nod2 has brought to light the significance of mononuclear cells as well as epithelial cells in inflammatory bowel disease (IBD) pathogenesis. Similarly, CCL20 is expressed in both mononuclear cells and epithelial cells and is likely to link innate and acquired immunity. We therefore asked whether CCL20 expression is altered in the peripheral blood mononuclear cells (PBMCs) from patients with ulcerative colitis (UC), a major type of IBD in Korea, and is correlated with the disease activity. The expression levels of CCL20 mRNA were significantly high in the PBMCs from the patients with UC. CCL20 protein expression was also up-regulated in the mucosal epithelium in UC but not in normal controls. Interestingly, however, disease activity index (DAI) revealed that untreated UC groups express higher expression levels of CCL20 mRNA than treated UC groups, implying that CCL20 may be a potential target for the anti-inflammatory treatments. In an agreement with this, three months follow up study revealed that the UC patients who were treated with 5-amino salicylic acid (5-ASA) and glucocorticoid showed dramatic decrease in their CCL20 mRNA levels as compared to untreated ones. Moreover, TNF-alpha-or IL-1beta-induced CCL20 secretion in human epithelial HT-29 cells was significantly diminished by the treatment with 5-ASA and/or dexamethasone, suggesting that CCL20 may be one of the central targets of the anti-inflammatory drugs. Collectively, these results suggest that CCL20 expression in UC may be associated with altered immune and inflammatory responses in the blood as well as the intestinal mucosa and further implied a potential for CCL20 as an important diagnostic marker for UC.

The Effect of Iron Depletion on the Monocytic Adhesion, Differentiation and SR-A Expression / 대한해부학회지

Maintenance of cellular iron homeostasis is a prerequisite for proliferation and differentiation of cells, and is also a central role in the regulation of immune function. Monocyte-macrophages play an important roles in host defense, particularly in the inflammatory process of acute and chronic disease. The reason that an iron is important in these cell is because an iron is indispensable in a generation of hydroxyl radical for bacterium killing. Because of the role of iron in the monocytic THP-1 cell differentiation is not become clear, we investigated whether THP-1 cell can differentiate to macrophage-like cell using of iron and iron chelator which cause iron depletion. The cell differentiation was not able to observe by iron treatment, by the way, the cell adhesion was increased in DFO treated monocyte and cellular pseodopodial extension, change of a nucleus-cytoplasmic ratio were showed in Differential interference contrast (DIC) and Giemsa staining, and it was inhibited by ferric citrate (FC). Increased polystyrene bead phagocytosis by DFO treatment of THP-1 cell were detected through FACS and rhodamine-phallodin staining. The SR-A expression, which was a cell differentiation marker, was increased by DFO treatment of THP-1 cell. These results suggest that iron depletion by DFO can promote THP-1 cell diffentiation into macrophage-like cell, and this may carrying out important role in the immune response.

Rebamipide Protects Colonic Damage Induced by Trinitrobenzene Sulfonic Acid (TNBS) via Down-Regulation of TNF-alpha IL-1beta and ICAM-1 / 대한해부학회지

During inflammation of the colon, cells of the gut mucosa produce or express numerous inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), and intercellular adhesion molecule 1 (ICAM-1). These mediators have been implicated as contributory factors to the inflammatory process, which results in colitis during inflammatory bowel disease (IBD). Rebamipide is an anti-gastric ulcer drug with anti-inflammatory properties in vivo and in vitro. The effects of Rebamipide on IBD have not been largely evaluated. Therefore, this study investigated the potential of Rebamipide to regulate the production of inflammatory mediators such as TNF-alpha, IL-1beta, and ICAM-1. Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis (IBD animal model), were treated intrarectally with 2 mM Rebamipide. Body weight, macro- and micro-histological scores, and activity were evaluated. As an index of tissue edema, the thickness of the colonic wall was measured between the serosal surface and the luminal surface of the mucosa. TNF-alpha, IL-1 beta, and ICAM-1 were detected by immunohistochemical staining. Rebamipide treatment of mice exhibiting TNBS-induced colitis dramatically improved the clinical and histopathological findings of inflammation. In addition, Rebamipide suppressed TNF-alpha, IL-1 beta, and ICAM-1 expression in TNBS-treated animals. Taken together, these findings suggest that Rebamipide is a potential therapeutic agent for treating patients with IBD.

Iron Chelator Induces MIP-3alpha/CCL20 in Human Intestinal Epithelial Cells: Implication for Triggering Mucosal Adaptive Immunity / 체질인류학회지

A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokie IL-8, in human intestinal epithelial cells(IECs). Microarray-based gene expression profiling revealed that iron chelator also induces CC chemokie MIP-3alpha/CCL20. As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as rhCCL20 at equivalent concentrations to attract CCR6+cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human Peripheral Blood Mononuclear Cells (PBMCs) and in THP-1 cells, but not in Human Umbillical Vein Endothelial Cells (HUVECs). Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.

Soluble factor from tumor cells induces heme oxygenase-1 by a nitric oxide-independent mechanism in murine peritoneal macrophages

Tumor target-derived soluble secretary factor has been known to influence macrophage activation to induce nitric oxide (NO) production. Since heme oxigenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress, we questioned whether soluble factor from tumor cells induces HO-1 through NO-dependent mechanism in macrophages. We designated this factor as a tumor-derived macrophage-activating factor (TMAF), because of its ability to activate macrophages to induce iNOS. Although TMAF alone showed modest activity, TMAF in combination with IFN-gamma significantly induced iNOS expression and NO synthesis. Simultaneously, TMAF induced HO-1 and this induction was slightly augmented by IFN-gamma. Surprisingly, however, induction of HO-1 by TMAF was not inhibited by the treatment with the highly selective iNOS inhibitor, 1400 W, indicating that TMAF induces the HO-1 enzyme by a NO-independent mechanism. While rIFN-gamma alone induced iNOS, it had no effect on HO-1 induction by itself. Collectively, the current study reveals that soluble factor from tumor target cells induces HO-1 enzyme in macrophages. However, overall biological significance of this phenomenon remains to be determined.

Total Hepatitis C Virus Core Antigen Assay for Hepatitis C Virus Viremia and Comparison with RNA Assay / 대한진단검사의학회지

BACKGROUND: Recently, trak - C (Total HCV core antigen test; Ortho Clinical Diagnostics, Raritan, NJ, USA) that is based on the enzyme- linked immnunosorbent assay was developed. So, we tried to compare the performance of the Hepatitis C virus (HCV) total core antigen test (HCVAg) with the qualitative in-house reverse transcription (RT) - polymerase chain reaction (PCR) assay and HCV- RNA Quantitation assay (HCVQn, Amplicor HCV monitor test version 2.0; Roche Diagnostics System, Basel, Switzerland). METHODS: Dilution test was performed to evaluate the reproducibility and detection sensitivity of the methods. 87 sera of 70 Hepatitis C virus antibody (Ab) positive patients were tested to evaluate the diagnostic sensitivity and concordance of three methods, and to discover the quantity relationship of HCVAg and HCVQn. We also contained the results of 100 negative control specimens by HCV Ag to evaluate the specificity. RESULTS: In the dilution test, the coefficient variation values of HCVAg were 41%, 29%, and 21% and HCVQn were 17%, 11%, and 150% of diluted sera respectively at 50, 5(-1), and 5(-2) dilution factor for four days running. The qualitative in - house HCV RT-PCR (5(-5) dilution factor) and HCVQn (5(-5) dilution factor) were more sensitive than the HCVAg (5(-2) dilution factor). And the diagnostic sensitivity was high in order on the qualitative in - house HCV RT-PCR; 97%, HCVQn; 91%, and HCVAg; 85%. The concordance rate between the three methods was 83.9%. The quantity of HCVAg and HCVQn showed a significant correlation (R =0.8, P<0.0001). CONCLUSIONS: HCVAg showed reliable results and a significant correlation with the quantitative RNA level. HCVQn showed a quantitative result but less sensitivity than the qualitative in-house HCV RT-PCR. Even though the HCVAg has slightly lower sensitivity than the two methods, methodologically, it is the most cost-effective, is simple, and gives high throughput. So it should be a simple economic surrogate marker for viremia detection and viral load monitoring.

The Function of Dimeric Structure of Soluble Intercellular Adhesion Molecule - 1 ( sICAM-1 ): Inhibition of Leukocyte Function Associated Antigen - 1 ( LFA-1 ) Binding to ICAM-3

Intercellular adhesion molecule-1 (ICAM-1) is a membrane protein, exists as a dimer on the cell surface, and interacts with leukocyte function associated antigen-1 (LFA-1), a member of beta2-integrin family. A soluble circulating form of ICAM-1 (sICAM-1) is also detected in human serum, and has been implicated as a regulator for LFA-1-dependent cell-cell interaction in vivo. However, previous reports demonstrated that sICAM-1 shows little inhibitory effect on LFA-1 binding to ICAM-l, indicating that sICAM-1 is unlikely to antagonize LFA-1/ICAM-1-mediated cellular events in vivo. Here, we investigated the property of the dimeric sICAM-1 as an inhibitor of LFA-1 interaction with ICAM-3, since the lower avidity of LFA-1 for ICAM-3 compared with ICAM-1 or ICAM-2 had been speculated. Using recently constructed heterodimeric sICAM-1 joined at the C terminus via an a-helical coiled coil (ACID-BASE) (Jun, CD. et al., 2001, Proc Natl Acad Sci 98, 6830-6835), we also tested whether the structural integrity in dimer could affect the inhibitory action of sICAM-1. Engineered sICAM-1 dimer that contained intact ectodomain (E34/E34) significantly blocked SKW3 cell (LFA-1+) binding to ICAM-3, but not to ICAM-1 and ICAM-2, indicating the lower avidity of LFA-1 to ICAM-3 than that of both ICAM-1 and ICAM-2. A one binding site knock out mutant (E34/K34) showed -2-fold reduction in efficiency compared with E34/E34 to inhibit cell binding. Interestingly, a one binding domain deletion mutant (E34/deltaD1-D2) showed significant reduction (~5-fold) compare with E34/K34, suggesting that structural integrity, which is precluded in E34/deltaD1-D2, is necessary for optimal binding of dimeric sICAM-1 to LFA-1, thereby inhibiting LFA-1/ICAM-3-dependent adhesion. Furthermore, BIAcore affinity measurements revealed that E34/deltaD1-D2 bound to immobilized soluble open LFA-1 I domain with an -3-fold reduced affinity compared with E34/K34. Overall, our results demonstrate that maintaining the structural integrity in dimer is necessary for optimal binding of sICAM-1 to LFA-1, and further suggest the therapeutic potential of dimeric sICAM-1 to antagonize LFA-1/ICAM-3-mediated cellular events in vivo.

Nitric oxide-induced immune switching in experimental inflammatory autoimmune diseases

BACKGROUND: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro-and anti-inflammatory effect s in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). MEHHOD: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)-or interphotoreceptor retinoid binding protein (IRBP)-immunized rat s could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiment s, the rat s were treated orally with MSDM (10 mg/kg/day) at the early stage (-1-4 days) or throughout the experimental period (-1-15 days). RESULTS: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development . A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP-or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-gamma. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rat s without MSDM secreted high concentrations of IFN-gamma, but low concentrations of IL-10. CONCLUSION: In conclusion, NO administation suppresses EAE and EAU by modulating the Th 1/Th2 balance during inflammatory immune responses. This work further suggest s that NO may be useful in the therapeutic control of autoimmune disease.

Comparative Effects of Paclitaxel and Nitric Oxide on Superficial Murine Bladder Tumor Cells / 대한면역학회지

No abstract available.

Patten of Expression of Collagen Genes in the Embryonic Human Mandible / 대한면역학회지

No abstract available.