• 한국동물위생학회지
• /
• 제25권4호
• /
• pp.371-376
• /
• 2002

To determine the effect of picolinic acid on NOㆍ production, murine macrophages were incubated with either medium, various concentrations of picolinic acid, or IFN-${\gamma}$ plus picolinic acid for 48 hr. Picolinic acid does not induce NOㆍ production by itself, it acted synergistically with INF-${\gamma}$ for the induction of reactive nitrogen intermediate production in murine macrophages. Thymidine incorporation appeared to be reciprocally related to nitrite levels, suggesting that IFN-${\gamma}$ plus picolinic acid induced NOㆍ synthesis exerted antiproliferative effects.

• 약학회지
• /
• 제51권4호
• /
• pp.270-276
• /
• 2007

Silybin is known to be a major active flavonoid component isolated from Silybum marianum, a hepatoprotective medicinal plant. In this study, we examined the immunomodulatory role of silybin on T cell and macrophage-mediated immune responses. To do this, the proliferation of splenic lymphocytes and CD8+ CTLL-2 cells under mitogenic stimulation with lipopolysaccharide (LPS), concanavalin (Con) A and interleukin (IL)-2 and the production of $TNF-{\alpha}$ and NO from LPS- and $IFN-{\gamma}$-activated macrophages was evaluated under silybin treatment. The mitogenic proliferation of splenic lymphocytes induced by LPS and Con A was strongly diminished by silybin in a dose-dependent manner. Moreover, the proliferation of CD8+ CTLL-2 cells was also negatively modulated by the compound. In contrast, silybin did not strongly suppress the proliferation of normal splenocytes and T cell line Sup-T1 cells, indicating that the inhibitory effect of silybin may be due to blocking only mitogenic responses of splenic lymphocytes. In addition, silybin inhibited $TNF-{\alpha}$ production in LPS-stimulated RAW264.7 cells. Effect of silybin however was distinct, according to NO-inducing stimuli. Thus, silybin only blocked NO production induced by $IFN-{\gamma}$ but not LPS and the inhibition was increased when PMA was co-treated with $IFN-{\gamma}$. Unlike NO inhibition, however, this compound protected the cytotoxic damage of RAW264.7 cells induced by both LPS and $IFN-{\gamma}$. Therefore, our data suggest that silybin may participate in host immune responses mediated by T cells and macrophages via regulating mitogenic proliferation, and the production of $TNF-{\alpha}$ and NO, depending on cellular stimuli.

• 한국임상수의학회지
• /
• 제27권6호
• /
• pp.640-646
• /
• 2010

네오스포라 감염증은 세포내성 원충성 기생충인 Neospora caninum에 의해 발생하는 질병으로 전세계적으로 발생하고 있으며, 소에서는 번식장해로 인한 막대한 경제적 손실을 유발한다. 본 연구는 4 곳의 각기 다른 목장으로부터 N. caninum에 자연 감염된 양성우와 음성우를 포함한 26두의 임신우를 선정하여 2주 내지 4주 간격으로 혈액을 채취하여 호르몬, 항체가, IFN${\gamma}$ 수준과 유산 혹은 분만과의 상관관계를 조사하였다. 유산하지 않은 Neospora 양성우14두의 S/P 평균값은 분만 전 15주에 최고치를 보였고, 이후 분만 때까지 감소하였다. 유산한 양성우 3두의 유산 시기는 각각 인공 수정 후 20주 (142일), 26주 (185일), 28주 (199일)였으며, 이들의 S/P값은 유산 전 13주부터 유산 때까지 높은 수준을 유지하였다. 유산하지 않은 양성우에서 IFN${\gamma}$ 수준은 개체에 따라 그리고 동일한 개체라도 임신기간이 경과함에 따라 다양하게 나타났으며, 유산한 양성우에서 IFN${\gamma}$ 수준은 계속 높은 상태를 유지하거나 또는 유산시점에 근접하여 급상승하였다. Neospora 음성우 9두의 IFN${\gamma}$ 수준은 양성우보다 낮았지만, 그 양상은 유산하지 않은 양성우와 유사하였다. 유산하지 않은 양성우와 음성우에서 평균적인 progesterone수준은 분만 전 7주부터 뚜렷하게 감소하였다. 유산한 양성우에서는 유산 전 5주와 7주의 평균적인 progesterone 수준은 정상 분만한 음성우나 양성우의 분만전 5주와 7주에 측정된 평균 progesterone 수준보다 낮았다. 유산한 양성우에서 17${\beta}$-estradiol의 평균 수준은 유산 시점에 근접할수록 증가하였지만, 혈청내 총양은 유산하지 않은 양성우와 음성우에서 분만시점에 근접하여 측정한 평균 17${\beta}$-estradiol 수준보다 더 낮았다. 이상의 결과로 미루어 보아 Neospora에 감염된 소에서 17${\beta}$-estradiol과 progesterone 수준의 저하는 IFN${\gamma}$ 산생을 증가시켜, 결국에는 유산을 초래할 수 있다고 생각된다.

• 한국식품영양학회지
• /
• 제24권1호
• /
• pp.65-70
• /
• 2011

This study was performed to investigate the in vitro effect of a corn water extract on immune function. Splenocyte proliferation was determined by the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl terazolium bromide) assay after preparing asingle cell suspension. Production of macrophage-secreted interleukin(IL)-$1{\beta}$, IL-6, and interferon(IFN)-${\gamma}$, was detected by ELISA using a cytokine assay kit. After a 48-hr incubation with mitogens(ConA or lipopolysaccharide), mice splenocyte proliferation increased with the addition of a corn water extract supplement at 10, 50, 100, 250, 500, or $1,000\;{\mu}g/m\ell$. Production of IL-$1{\beta}$, IL-6, and IFN-${\gamma}$ increased in treatments supplemented with the corn water extract. In an in vitro study, splenocyte proliferation increased when $50\sim1,000\;{\mu}\ell/m\ell$ corn water extract was added. In an ex vivo experiment, the highest production of cytokines by activated peritoneal macrophages was observed in mice orally administered 500 mg/kg body weight/day.

• 대한본초학회지
• /
• 제20권4호
• /
• pp.141-149
• /
• 2005

In order to investigate the immunomodulational effects of Lonicerae Caulis et Folium, the author measured cytokines production(IL-10, IL-12(P35), IL12(P40), $IFN-{\gamma}$) in mice splenocytes. The results were obtained as follows : 1. The water extract of Lonicerae Caulis et Folium significantly enhanced the gene expression of IL-12(P35), IL-12(P40), but reduced the gene expression of IL-10, $IFN-{\gamma}$. 2. In water fraction and ethyl acetate fraction, the gene expression of IL-12(P35), $IFN-{\gamma}$ was significantly increased and that of IL-12(P40), IL-10 was decreased. The above results demonstrate that Lonicerae Caulis et Folium has enhancing immune activity by upregulation of these cytokines. Therefore, if we make the relationship between these cytokines(IL-10, IL-12, $IFN-{\gamma}$) besides IL-1, IL-4, IL-6, $TNF-{\alpha}$, IL-8, $TGF-{\beta}$ and so on which concerned the immunopotentiation, the immunopotentiational mechanism of Lonicerae Caulis et Folium will be shown clearly.

• IMMUNE NETWORK
• /
• 제3권1호
• /
• pp.53-60
• /
• 2003

Background: The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-${\alpha}$. Recently, macrophage also can produce the INF-${\gamma}$ that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-${\alpha}$ can modulate the INF-${\gamma}$ production in the macrophages from tumor environment as a part of tumor angiogenic switch. Methods: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. $Mac1^+$-macrophages were purified using magnetic bead ($MACs^{TM}$; Milteny Biotech, Germany) and cultured with various concentrations of TNF-${\alpha}$ for various time points at $37^{\circ}C$. The supernatants were analyzed for IFN-${\gamma}$ or VEGF by ELISA kit (Endogen, Woburn, MA). Results: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-${\alpha}$ to produce INF-${\gamma}$. However, the cells from tumor environment produced IFN-${\gamma}$ as well as VEGF and upregulated by the addition of LPS or TNF-${\alpha}$. RT-PCR analysis revealed the external TNF-${\alpha}$-induced IFN-${\gamma}$ gene expression in the macrophages from tumor environment. Conclusion: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-${\alpha}$ might be a key cytokine in tumor angiogenic switch.

• The Korean Journal of Physiology and Pharmacology
• /
• 제5권1호
• /
• pp.55-63
• /
• 2001

In macrophages, lipopolysaccharide (LPS) alone or in combination with $interferon-{\gamma}\;(IFN-{\gamma})$ has been shown to release a nitric oxide (NO) through the increase of the transcription of the inducible nitric oxide synthase (iNOS) gene. To investigate the exact intracellular signaling pathway of the regulation of iNOS gene transcription by LPS plus $IFN-{\gamma},$ the effects of protein tyrosine kinase (PTK) inhibitor and protein kinase C (PKC) inhibitors on NO production, iNOS mRNA expression, nuclear $factor-_{\kappa}B\;(NF-_{\kappa}B)$ binding activity and the promoter activity of iNOS gene containing two $NF-_{\kappa}B$ sites have been examined in a mouse macrophage RAW 264.7 cells. LPS or $IFN-{\gamma}$ stimulated NO production, and their effect was enhanced synergistically by mixture of LPS and $IFN-{\gamma}.$ The PTK inhibitor such as tyrphostin reduced LPS plus $IFN-{\gamma}-induced$ NO production, iNOS mRNA expression and $NF-_{\kappa}B$ binding activity. In contrast, PKC inhibitors such as H-7, Ro-318220 and staurosporine did not show any effect on them. In addition, transfection of RAW 264.7 cells with iNOS promoter linked to a CAT reporter gene revealed that tyrphostin inhibited the iNOS promoter activity through the $NF-_{\kappa}B$ binding site, whereas PKC inhibitors did not. Taken together, these suggest that PTK, but not PKC pathway, is involved in the regulation of the iNOS gene transcription through the $NF-_{\kappa}B$ sites of iNOS promoter in RAW 264.7 macrophages by LPS plus $IFN-{\gamma}$.

• 약학회지
• /
• 제43권4호
• /
• pp.474-480
• /
• 1999

The purpose of this study is to define whether Asterina pectinifera Lectin (APL) is effective on the cytokine production. Isolated mRNA from hPBMC (human peripheral blood mononuclear cells) stimulated with APL for various reaction times (1 to 96 hours) was detected by RT-PCR. The intensity of band for IL-1 and $IFN{\gamma}$ mRNA was markedly increased at l hour, and IL-2 mRNA was strongly expressed at 4 hours. The mRNA band of APL-induced IL-2 and $IFN{\gamma}$ was weaker than that of IL-1, IL-6 and $TNF{\alpha}$. The mRNA expression of 4 cytokines (IL-1, IL-2, $IFN{\gamma}$ and $TNF{\alpha}$) was detected up to 48 hours, and that of IL-6 was detected until 72 hours. ELISA was used to look protein secretion of the cytokine gene with IL-1, IL-2 and TNF$\alpha$expressed strongly in RT-PCR. The highest protein secretion was at 4 hours with IL-1, at 8 hours with IL-2 and at 4 hours with $TNF{\alpha}$. These results suggest that APL can induce the production of some cytokines and the immune response from PBMC was done within the first few hours of stimulation with APL.

• 대한치과교정학회지
• /
• 제25권6호
• /
• pp.689-696
• /
• 1995

Effects of several cytokines($IL-1{\beta},\;TNF_{\alpha},\;and\;IFN_{\gamma}$) have been examined on fetal rat osteoblast-like cells. To investigate whether cytokines play direct causal roles in production of lysosomal enzyme, fetal rat osteoblast-like cells were treated with $IL-1{\beta},\;TNF_{\alpha},\;and\;IFN_{\gamma}$, respectively or combined. And acid phosphatase was determined by biochemical method. Alkaline phosphatase was assayed to determine the effects of $IL-1{\beta},\;TNF_{\alpha},\;and\;IFN_{\gamma}$ on the expression of this enzyme. And also experiment of calcified nodule formation was performed to assess the effects of cytokines on the bone-forming activity of osteoblast-like cells in vitro. Acid phosphatase activity was significantly increased by the addition of $IL-1{\beta}\;and\;TNF_{\alpha}$, whereas decreased by $IFN_{\gamma}$. However, no significant change:: in alkaline phosphatase activity was observed when the osteoblast-like cells were treated with $IL-1{\beta}\;and\;TNF_{\alpha}$. Interestingly, $IFN_{\gamma}$ showed stimulatory effect on alkaline phosphatase activity. The number of calcified nodules was decreased by treatment of cultures with 1 ng/ml $IL-1{\beta},\;20\;ng/ml\;TNF_{\alpha}$, and 500 u/ml $IFN_{\gamma}$ continuously for 21 days, while considerable number of calcified nodules were formed in control group of osteoblast-like cell in culture for 21 days. These results seem to suggest that cytokines may play crucial roles in bone remodeling through the direct action on the osteoblast-like cell.

• 대한한방내과학회지
• /
• 제25권2호
• /
• pp.245-257
• /
• 2004

This study was done to evaluate the antiallergic effects of Naenghyohwan(NHH). Cytotoxic activity for lung fibroblast cells, cytokines transcript expression of IL-1, IL-4, IL-5, TNF-${\alpha}$, IL-6, IL-10, TGF-${\beta}$1, IFN-${\gamma}$, production of IL-4, IL-10. IFN-${\gamma}$, IgE in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells and the production of histamin released in mast cells, and the expression of histamine release factor(HRF) in splenic B cells were measurd. The following results were obtained. NHH did not showed cytotoxicity in fibroblast cells. NHH increased the gene synthesis of TNF-${\alpha}$, IFN-${\gamma}$(m-RNA). NHH decreased the gene synthesis of IL-1${\beta}$, IL-4, IL-5, IL-6, TGF-${\beta}1$(m-RNA). NHH decreased the appearance of IL-4, IgE significantly. NHH increased the appearance of IL-10. IFN-${\gamma}$ significantly. NHH decreased the proliferation of B cells significantly. NHH decreased the appearance of histamin expression of HRF in mast cells significantly. The results suggest NHH is effective against the allergies. Continued studies of the antiallergic effects of NHH are urged.