• IMMUNE NETWORK
• /
• 제11권6호
• /
• pp.412-415
• /
• 2011

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the $H-2K^b$-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.

• IMMUNE NETWORK
• /
• 제7권4호
• /
• pp.197-202
• /
• 2007

Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

• Biomolecules & Therapeutics
• /
• 제21권1호
• /
• pp.35-41
• /
• 2013

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

• IMMUNE NETWORK
• /
• 제14권6호
• /
• pp.328-332
• /
• 2014

Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.

• Natural Product Sciences
• /
• 제19권4호
• /
• pp.347-354
• /
• 2013

Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of cordycepin on the antigen-presenting function of antigen-presenting cells (APCs). Dendritic cells (DCs) were cultured in the presence of cordycepin and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through RT-PCR and Western blot analysis. Cordycepin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of cordycepin was also confirmed using mice that had been injected with cordycepin followed by soluble OVA. Furthermore, cordycepin suppressed the mRNA and protein levels of iNOS, COX-2, pro-inflammatory cytokines in a concentration-dependent manner. These results provide an understanding of the mechanism of the T cell response-regulating activity of cordycepin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

• IMMUNE NETWORK
• /
• 제10권4호
• /
• pp.135-143
• /
• 2010

Background: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). Methods: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. Results: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. Conclusion: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.306.2-306.2
• /
• 2002

The main targets for the immunosuppressive calcineurin inhibitors. tacrolimus (FK-506) and cyclosporine A (CsA). have been considered to be activated T cells. but not antigen presenting cells (APCs). In the present study. we examined the effects of these drugs on the MHC-restricted presentation of exogenously added antigen. ovalbumin (OVA). in dendritic cells (DCs). Particulate form of OVA was efficiently captured. processed and presented on class I MHC molecules (cross-presentation) as well as on class II MHC molecules. (omitted)

• Biomolecules & Therapeutics
• /
• 제19권1호
• /
• pp.77-83
• /
• 2011

Sulforaphane is an isothiocyanate found in cruciferous vegetables that has been reported to be an effective cancer preventive agent inducing growth arrest and/or cell death in cancer cells of various organs. This paper reports that sulforaphane exerts immunomodulatory activity on the MHC-restricted antigen presenting function. Sulforaphane efficiently increased the class II-restricted presentation of an exogenous antigen, ovalbumin (OVA), in both dendritic cells (DCs) and peritoneal macrophages in vitro. The class II-restricted OVA presentation-enhancing activity of sulforaphane was also confirmed using mice that had been injected with sulforaphane followed by soluble OVA. On the other hand, sulforaphane did not affect the class I-restricted presentation of exogenous OVA at concentrations that increase the class II-restricted antigen presentation. At a high concentration ($20\;{\mu}M$), sulforaphane inhibited the class I-restricted presentation of exogenous OVA. Sulforaphane did not affect the phagocytic activity of the DCs, and the cell surface expression of total H-$2K^b$, B7-1, B7-2 and CD54 molecules, even though it increased the expression of I-$A^b$ molecules to a barely discernable level. These results show that sulforaphane increases the class II-restricted antigen presenting function preferentially, and might provide a novel insight into the mechanisms of the anti-cancer effects of sulforaphane.

• 한국어병학회지
• /
• 제27권1호
• /
• pp.1-9
• /
• 2014

저수온기만 넙치에 대량 폐사를 일으키는 바이러스성 출혈성 패혈증을 폐사가 발생하는 $15^{\circ}C$, 폐사가 발생하지 않는 $20^{\circ}C$에서 인공감염시켜 넙치의 면역 유전자 발현 profile을 cDNA microarray 분석하였으며, 특히 저수온기에 폐사가 나타나는 원인을 면역 유전자 발현과 관련시켜 알아보고자 하였다. $15^{\circ}C$, $20^{\circ}C$의 감염 세포구에 공통으로 발현되는 유전자는 MHC class I, IL-8, myeloperoxidase 및 endonuclease G-like 유전자로 모든 세포표면에 존재하여 항원을 제시하거나 호중구 주화성을 자극하는 유전자들이었다. 항원 가공 및 제시, 항체 생성에 관여하는 MHC class II, immunoglobulin (Ig)과 retinoblastoma 등의 유전자는 $20^{\circ}C$에서는 발현이 증가하였으나 $15^{\circ}C$에서는 발현이 감소되었다. 이로부터 폐사가 발생하지 않는 $20^{\circ}C$는 바이러스 감염초기의 항원 제시, MHC class I과 II에 의한 항원제시, apoptosis 및 이후의 항체 생산이 정상적으로 이루어져 폐사가 발생하지 않는 것으로 생각되었다. 그러나 폐사가 발생하는 $15^{\circ}C$에서는 MHC class I매개의 항원 제시와 탐식 작용등의 선천 면역은 이루어지나 macrophage에 의한 MHC class II매개의 항원 제시와 apoptosis저하, 항체 생산 관련 유전자의 발현저하가 관찰되어 초기 macrophage에 의한 항원제시의 실패로 적응 면역이 제대로 활성화되지 않아 폐사가 발생한 것으로 사료된다.

• BMB Reports
• /
• 제30권6호
• /
• pp.415-420
• /
• 1997

Although $CD4^+$ T cell responses to protein-derived antigen have well been understood, the epitopes recognized by hapten-specific $CD4^+$ T cells have not been fully defined. In this study, we characterized the response of a T cell hybridoma (5Di0.1B8) which is specific for a hapten. N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) restricted by MHC class II $I-A^d$. Using three different antigen presenting cells (APCs) expressing $I-A^d$, the role of class II MHC proteins in haptenic antigen presentation and subsequent activation of 5D10.1B8 has been examined. Activation of 5D10.1B8 T cells by HSAB analogs was also performed. Our results show that each APC activated T cells differentially and that interleukin-2 (IL-2) augmented antigen-presenting ability of all the APCs, suggesting that increased expression of class II MHC protein by IL-2 played an important role in HSAB presentation and T cell activation. Finally, early T cell receptor-dependent signals induced by HSAB or its analogs were examined by phosphotyrosine immunoblot analysis, and showed that tyrosine phosphorylation level of a 18-20 kD protein increased upon stimulation.