• IMMUNE NETWORK
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• v.9 no.6
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• pp.255-264
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• 2009

Background: Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine. Methods: We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change. Results: LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naive macrophages, through the treatment with high concentrations of cordycepin ($40{\mu}g/ml$). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and chemokines (CX3CR1, RANTES), such as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-${\beta}$) were up-regulated by both cordycepin and adenosine. Conclusion: Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.135-143
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• 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.

• International Journal of Oral Biology
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• v.41 no.1
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• pp.1-8
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• 2016

OSCC is currently the most common malignancy of the head and neck, affecting tens of thousands of patients per year worldwide. Natural flavonoids from plants are potential sources for novel anti-cancer drugs. Icariin is the active ingredient of flavonol glycoside, which is derived from the medical plant Herba Epimedii. A metabolite of icariin, icariside II exhibits a variety of pharmacological actions, including anti-rheumatic, anti-depressant, cardiovascular protective, and immunomodulatory functions. However, the exact mechanism causing the apoptosis-inducing effect of icariside II in OSCC is still not fully understood. In the present study, we assessed the anti-cancer effect of icariside II in OSCC cell lines by measuring its effect on cell viability, cell proliferation, and mitochondria membrane potential (MMP). Icariside II treatment of OSCC cells resulted in a dose- and time-dependent decrease in cell viability. Hoechst staining indicated apoptosis in icariside II-treated HSC cells. Icariside II inhibited cell proliferation and induced apoptosis in HSC cells, with significant increases in all present parameters in HSC-4 cells. The results clearly suggested that icariside II induced apoptosis via activation of intrinsic pathways and caspase cascades in HSC-4 cell lines. The collective findings of the study suggested that Icariside II is a potential treatment for OSCC; in addition, the data could provide a basis for the development of a novel anti-cancer strategy.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.18 no.1
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• pp.153-163
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• 1996

Macrophage inflammatory protein $(MIP)-1{\alpha}$ is a cytokine which produces wide range of bioactivities such as proinflammatory, immunomodulatory, and hematopoietic modulatory actions. To determine whether $MIP-1{\alpha}$ acts as a negative regulator on the functions of lymphocyte, $[^3H]$-thymidine incorporation test and flow cytometric analysis were performed by using human tonsil T cell, human peripheral blood T cell, and murine cytolytic T lymphocyte (CTL) line CTLL-2, The results were as follow. 1. When human tonsil T lymphocytes were stimulated with anti-CD3 monoclonal antibody (mAb), rate of T cell proliferation was about four times increased. 200ng/ml of $MIP-1{\alpha}$ inhibited anti-CD3 mAb-mediated T cell growth as much as 60% (P<0.05). 2. The suppression of human peripheral T cell proliferation produced by $MIP-1{\alpha}$ was dramatic, but variable among T cells derived from different individuals $(40%{\sim}90%)$. 3. $MIP-1{\alpha}$inhibited the proliferation of murine CTL line CTLL-2 as much as 75%(P<0.001). 4. When the $MIP-1{\alpha}$ was added to human peripheral T cell, cell proporation of $CD4^+$ helper T cell and $CD8^+$ CTL were not noticeably affected. The expression level of CD4, not of Cd8, however, was down regulated by $MIP-1{\alpha}$ treatment $(27%{\sim}82%)$.

• Journal of Veterinary Clinics
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• v.26 no.1
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• pp.1-7
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• 2009

The Artemisia capillaris THUNB is a perennial herb that belongs to the family Compositae spp and probably the most common plant among the various herbal folk remedies being used in the treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. Recently the biological and pharmacological actions of herb have been studied well such as antibacterial, antidiabetic and antitumor activities. This experiment was conducted to investigate antitumor and immunomodulatory effects of Artemisia capillaris extracts against Hepa-1c1c7 and Sarcoma 180 cancer cells in in vivo experimental tests. In in vivo experimental tests using 210 ICR mice, based on flow cytometry, CD3+, CD4+, CD8+ and TNF-${\alpha}+$ splenocytes were significantly (p<0.05) reduced in the Hepa-1c1c7 and Sarcoma 180 inoculated vehicle controls, HP and SP, compared to those of the intact vehicle control on both the $28^{th}$ day and the $42^{nd}$ day, respectively. These decreases of CD3+, CD4+, CD8+ and TNF-${\alpha}+$ cells induced by tumor inoculations were significantly (p<0.05) inhibited by mACH treatment regardless of the type of experiments and tumor cells inoculated. The results suggest that Artemisia capillaris methanol extracts have prominent antitumor effects on the cancer cell lines Hepa-1c1c7 and Sarcoma 180.

• Journal of Periodontal and Implant Science
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• v.24 no.3
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• pp.472-482
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• 1994

Cytokines expressed specifically in leukocytes subsets and in activated cells, which are involved in chemotaxis and activation of leukocytes, are recently defined as chemokines. Macrophage inflammatory $protein-1{\alpha}(MIP-1{\alpha})$ and $MIP-1{\beta}$ are members of C-C chemokine subfamily which produces wide immunomodulatory, proinflammatory, and hematopoietic modulatory actions. We have studied their gene expression by using Northern blot analysis in various blood cells such as cytolytic T lymphocyte(CTL), helper T lymphocyte(HTL), macrophage, and B lymphocyte. Resting CTL line CTLL-R8 expressed $MIP-1{\alpha}$ mRNA which was downregulated by ConA stimulation. Both of resting and ConA stimulated HTL line Hut78 and Jurkat did not express $MIP-1{\alpha}$ mRNA. There was detectable $MIP-1{\alpha}$ transcript in HTL hybridoma 2B4.11 which was a little upstimulated by ConA stimulation. B cell line 230, and macrophage cell line RAW264.7 and WR19M.1 showed distinct $MIP-1{\alpha}$ message which were induced after LPS stimulation. Expression pattern of $MIP-1{\beta}$ in all cell lines or cell were almost identical to that of $MIP-1{\alpha}$. Also strategies employed to identify and characterize the biological functions was preceded by receptor cloning to trace the shorcut to the final goal of cytokine research. For the cloning of $MIP-1{\alpha}$ receptor(R), we used synthetic oligonucleotides of transmembrane(T) conserved sequences of already cloned human(h) IL-8-R, and performed reverse transcription-polymerase chain reaction(RT-PCR) amplification using murine(m) macrophage cell line mRNA. Among 5RT-PCR products, we isolated a homologous cDNA with hIL-8-R which were shown to be putative mIL-8-R cDNA.

• Journal of Veterinary Clinics
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• v.24 no.3
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• pp.372-378
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• 2007

The Artemisia capillaris THUNB is a perennial herb that belongs to the family Compositae spp and probably the most common plant among the various herbal folk remedies being used in the treatment of abdominal pain hepatitis chronic liver disease, jaundice and coughing in Korea. Recently the biological and pharmacological actions of herb have been studied well such as antibacterial, antidiabetic and antitumor activities. This experiment was conducted to investigate antitumor and immunomodulatory effects of Artemisia capillarix extracts against Hepa-1c1c7 and Sarcoma 180 cancer cells on in vivo experimental tests. On in vivo experimental tests using 280 ICR mice the gain of body weight in the control-group mice bearing Sarcoma 180 ascites tumor was 1.5 times more than that of the normal-group mice after 33 days. However, the gain of body weight in all experimental groups administered with Artemisia capillaris extracts was significantly lower than that of the control-group mice (P<0.05). The mean survival times of mice administered with Artemisia capillaris extracts of 25 and 100 mg/kg for 28 days were shown to be 25.39% and 15.39% longer than that of the control-group mice injected with saline (P<0.05). Artemisia capillaris extracts showed the highest tumor inhibition effects, which were 42.4% and 27.2% when intraperitoneally injected with doses of 25 and 100 mg/kg once a day for 28 days in inoculated ICR mice with Sarcoma 180 solid tumor cells (P<0.05). The results suggest that Artemisia capillaris methanol extracts have prominent antitumor effects on the cancer cell lines Hepa-1c1c7 and Sarcoma 180.

• The Korea Journal of Herbology
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• v.24 no.3
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• pp.161-167
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• 2009

Objectives : Maekmoondong-tang (MMDT), a Korean herbal medicine, has been used to treat severe dry cough in patients with bronchitis and pharyngitis. MMDT has been reported to have anti-inflammatory, anti-allergic, immunomodulatory, secretory-modulating, and metabolic regulatory actions. However, there are no evidence in regard to the effects of MMDT on carcinogenesis and metastasis. Here, we investigated the effects of 70% ethanol extract of MMDT on cell viability, apoptosis, and motility in human hepatocarcinoma HepG2 cells. Methods : Cell viability was measured using the CCK-8 assay, and the apoptosis induction was evaluated by caspase-3 activity. To detect apoptotic features, the cells treated with MMDT were stained with 4'-6-diamidino-2-phenylindole (DAPI). Cell motility was examined by Boyden chamber assay and Real-time Cell Index of Migration assay. Gelatin zymography also performed to measure matrix metalloproteinase (MMP)-2/9 activity. Results : We found that MMDT significantly inhibited cell proliferation and increased caspase-3 activity in a dose-dependent manner in HepG2 cells. Apoptotic features such as chromatin condensation and apoptotic bodies were observed in MMDT-treated cells by DAPI staining. MMDT also suppressed PMA-induced cell motility and activities of MMP-2/9. Conclusions : Our results exhibited that MMDT possess the anti-carcinogenetic and anti-metastatic activities via caspase-3 activation and down-regulation of cell motility and invasion in HepG2 cells. Therefore, these findings suggest that MMDT could be potentially applied to the prevention and treatment of cancer.