• IMMUNE NETWORK
• /
• 제5권2호
• /
• pp.68-77
• /
• 2005

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

• IMMUNE NETWORK
• /
• 제3권1호
• /
• pp.61-68
• /
• 2003

Background: Fibroblast functions both as a structural element and as a vital immunoregulatory cell. Fibroblasts regulate inflammation through governing of chemokine expression. In order to elucidate the mechanisms by which the expressions of chemokines were regulated, the co-stimulatory effects of Th1 and proinflammatory cytokines were compared using nasal mucosal fibroblasts. Methods: Human nasal mucosa was obtained from surgery for septal deviation and the growth of fibroblasts was established. Fibroblasts from 4th to 6th passage were stimulated with various combinations of cytokines. To inhibit selected signaling pathways, fibroblasts were pretreated with cyclosporin A, wortmannin, staurosporine, and dexamethasone prior to the stimulation with cytokines. The supernatants were collected and chemokines were detected with a sandwich enzyme-linked immunosorbent assay. Results: $TNF-{\alpha}/IFN-{\gamma}$-induced production of RANTES was inhibited by all inhibitors used. MCP-1 was produced constitutively and $TNF-{\alpha}$-induced or $TNF-{\alpha}/IFN-{\gamma}$-induced production of MCP-1 was not inhibited by cyclosporin A or wortmannin, but by stauroporine or dexamethasone. All inhibitors used in this experiment inhibited $TNF-{\alpha}/IFN-{\gamma}$-induced or $IL-1{\beta}/IFN-{\gamma}$-induced production of MCP-2 in nasal mucosal fibroblasts. Although staurosporine or dexamethasone showed strong inhibitory effects, cyclosporin A or wortmannin did not inhibit the production of MCP-3 by $IL-1{\beta}/IFN-{\gamma}$ treatment. Conclusion: Chemokines were strongly induced by stimulation of cytokines in combination and showed different pattern of inhibition by the inhibitors. Therefore, it was assumed that cytokines acted on multiple pathways or on unknown pathways which converged to gene-specific transcription factors.

• Preventive Nutrition and Food Science
• /
• 제12권3호
• /
• pp.148-153
• /
• 2007

Obesity-induced inflammation plays a crucial role in obesity-related pathologies such as type II diabetes and atherosclerosis. Adipose tissue macrophages and the cell-derived proinflammatory chemokines are key components in augmenting inflammatory responses in obesity. Anthocyanins such as cyanidin and $cyanidin-3-O-{\beta}-D-glucoside$ (C3G) are known to elicit anti-inflammatory activities by suppressing the production of proinflammatory mediators such as tumor necrosis factor alpha and nitric oxide in LPS-stimulated macrophages. In the present study, we investigated whether cyanidin and C3G have the potential to suppress the inflammatory responses of adipose cells. Cyanidin and C3G not only suppressed the migration of RAW 264.7 macrophages induced by mesenteric adipose tissue-conditioned medium, but also inhibited the activation of the cells to produce inflammatory chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-related protein-2 (MRP-2) in a dose-dependent manner. Cyanidin and C3G also inhibited the release of MCP-1 and MRP-2 from adipocytes and/or macrophages. These findings suggest that cyanidin and C3G may suppress the inflammatory responses of adipose tissue in obesity.

• ALGAE
• /
• 제22권4호
• /
• pp.333-338
• /
• 2007

A fucoidan, isolated from Korean Undaria pinnatifida spoprophyll (UP-F), was investigated for its immunomodulating activity on murine macrophages and splenocytes, and its activity was compared with that of fucoidan from Fucus vesiculosus (FV-F). Treatment of UP-F resulted in inhibition of the growth of murine macrophage RAW 264.7 cells, but its cytotoxicity was not observed in normal murine splenocytes. FV-F was shown to be highly cytotoxic to both immune cells, and its cytotoxic activity was higher than that of UP-F. Treatment of UP-F induced TNF-α in a dose-dependent manner from two types of macrophages, RAW 264.7 cells and murine peritoneal macrophages. The TNF-α-inducing activity of UP-F was higher than that of FV-F. UP-F also actively induced chemokines (RANTES and MIP-1α) from RAW 264.7 cells. Furthermore, treatment of UP-F gave rise to activation of murine splenocytes to produce cytokine (IL-6) and chemokines (RANTES and MIP-1α), showing significantly higher activity than that of FV-F. These results indicate that UP-F is less cytotoxic to immune cells than FV-F, and possesses immunomodulating activity to produce cytokines and chemokines from macrophages and splenocytes.

• Journal of Yeungnam Medical Science
• /
• 제20권2호
• /
• pp.187-196
• /
• 2003

The cytokines are the hormone-like proteins, which are produced in the mononuclear cells. They have many roles, such as immune mediators, cell differentiations, angiogenesis. The chemokines have chemotactic effects which control the host immune response. There were few reports about the cytokines associated with musculoskeletal tumors. From late 1980s, the cytokine studies of bone tumors such as osteosarcoma were started, but most studies for benign and malignant musculoskeletal tumors were left to be explored. To evaluate the characteristics of the cytokines in variable musculoskeletal tumors, tissues were obtained from the seven patients who visited the Yeungnam University hospital from February to July 2000. They were lipoma (1 case), parosteal osteoma (1 case), enchondroma (2 cases), pigmented villonodular synovitis (1 case), ganglion (1 case), and metastaic squamous cell carcinoma (1 case). The gene experession of the cytokines were analyzed by RNase protection assay (RPA) and reverse transcription-polymerase chain reaction (RT-PCR). The lipoma and parosteal osteoma expressed MIP-$1{\beta}$, and IP-10 genes. The two enchondromas showed different results, one expressed all of MIP-$1{\alpha}$, MIP-$1{\beta}$ and IP-10 genes but the other expressed none of above. The pigmented villonodular synovitis strongly expressed MIP-$1{\alpha}$ and IP-10 when compared with the other cases. The ganglion did not express all of the chemokines mentioned above. And the metastatic squamous cell carcinoma expressed all of the chemokines and especially IP-10 was highly expressed. Even though this study has only a few cases, these results provide a basis for the cytokine mediating network study in musculoskeletal tumors.

• Journal of Acupuncture Research
• /
• 제20권4호
• /
• pp.53-65
• /
• 2003

Although the effect of Bee Venom has been reported, its mechanism has not been fully elucidated. Nitric Oxide(NO) is one of the free radicals and mediates in inflammation diseases. Chemokines contribute to the pathogenesis of several disorders such as allergic rhinitis and rheumatoid arthritis and so on. The objective of this study was to investigate the scavenging effect of Bee Venom on NO and on expression of chemokine genes. There was no significant NO scavenging effect in Crude Bee Venom, Apamin, Melittin, and MCD-peptide. The expression of chemokines was examined by RT-PCR using the human mast cell line(HMC-1), which is known to secrete and express chemokines. In order to investigate the protective effect of Bee Venom, HMC-1 cells were incubated with pretreatment of Bee Venom for 24 hrs and stimulated with 1 uM calcium ionophore A23178 for 2 hrs. RT-PCR analyses of chemokine genes showed that expressions of RANTES and MCP-1 were increased compared to the calcium ionophore-only treated group. But IL-8 and MCP-3 did not express increasing effect compared to control group. This study may provide important basic data on the possibility of the clinical treatment of Bee Venom in inflammation diseases.

• 대한의생명과학회지
• /
• 제20권3호
• /
• pp.162-167
• /
• 2014

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.

• Journal of Yeungnam Medical Science
• /
• 제24권2호
• /
• pp.129-136
• /
• 2007

2002년 1월 1일부터 6월 30일까지 비재발성 또는 약한 재발성 마른기침을 주증상으로 영남대학교 의료원 소아과를 내원한 환아들 중 연구의 목적에 동의한 소아를 대상으로 이들에서의 케모카인 IFN-${\gamma}$-inducible protein 10 (IP-10), Macrophage cationic protein 1 and 3 (MCP-1, 3), Interleukin (IL)-8, RANTES, eotaxin 및 Gro-${\alpha}$의 발현 양상을 알아보았다. 1) 대상 환아는 모두 6명(남 3명, 여 3명)으로, 평균 연령은 73.2개월(34개월~122개월)이었다. 2) 케모카인 IP-10, MCP-3는 모든 환아에서, RANTES는 5명에서, IL-8은 3명에서 발현되었다. 3) Eotaxin, Gro-${\alpha}$ 및 MCP-1은 모든 환아에서 전혀 발현되지 않았다. 4) 추적 관찰에 응한 1례에서 회복기에 MCP-3, RANTES 및 IL-8 발현의 감소가 관찰되었다. 단순 기침 환아에서 케모카인 MCP-3, RANTES 및 IL-8 등이 매우 중요한 역할을 하는 것으로 확인되었다. 향 후 이에 관한 더 많은 비교 연구가 필요할 것으로 생각한다.

• 동의생리병리학회지
• /
• 제24권2호
• /
• pp.258-265
• /
• 2010

Atopic dermatitis (AD) is a chronically relapsing pruritic inflammatory skin disease. To find new anti-inflammatory products for skin inflammatory disease such as AD and contact dermatitis, we produced the effective microorganism fermentation substance (EM-S) by fermentation of medicinal plants with effective microorganisms including photosynthetic bacteria, lactic acid bacteria and yeast, screened the effects of EM-S on NC/Nga model mice. Murine AD-like skin lesions were made by painting Dermatophagoides farinae (Df) extract. Topically applied EM-S significantly reduced clinical severity score, ear thickness and histological grade in AD-like NC/Nga mouse model by Df antigen sensitization. In addition, the serum IgE and Th2 chemokine levels (TARC/CCL17, MDC/CCL22 and CTACK/CCL27) were significantly reduced by EM-S. Futhermore, skin tissue expressions of Th2 chemokines were significantly reduced by EM-S. These results demonstrate that topical application of EM-S may be improve the AD-like skin lesion by suppressing IgE and Th2 chemokines.

• Biomolecules & Therapeutics
• /
• 제16권4호
• /
• pp.394-402
• /
• 2008

Atopic dermatitis (AD) is an inflammatory skin disease commonly characterized by infiltration of inflammatory cells into skin lesions. Keratinocytes produce many chemokines that are involved in the pathogenesis of skin disorders. In particular, macrophage-derived chemokine (MDC/CCL22) and thymus and activationregulated chemokine (TARC/CCL17) are Th2-type cytokines. Serum MDC and TARC levels are increased in AD patients. In this study, we investigated the anti-inflammatory effect and mechanism of action of the active fraction from Prunus yedoensis bark. We evaluated their inhibitory effects on the AD-like inflammatory markers (MDC and TARC) and JAK-STAT pathway (STAT1) in HaCaT keratinocytes. The EtOAc fraction of the crude extract (80% EtOH) and the E5 sub-fraction potently inhibited the induction of MDC and TARC mRNA and protein at 50 ${\mu}g$/mL in HaCaT cells. In addition, the E5 sub-fraction inhibited the phosphorylation of STAT1 protein associated with IFN-$\gamma$ signaling transduction in a dose-dependent manner. Thus, P. yedoensis may have antiatopic activity by suppressing the inflammatory chemokines (MDC and TARC).