• Preventive Nutrition and Food Science
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• 제15권1호
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• pp.19-23
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• 2010

This study examined the effects of Acrylamide (ACR) and L-ascorbic acid (AsA) on the proliferation of splenocytes and the mitogen-stimulated lymphocyte proliferation in young (8 weeks) and aged (82 weeks) C57BL/6male mice in vitro. AsA increased splenocyte proliferation in both groups; however, this effect was higher in old mice, while the proliferation of lymphocyte was decreased except for treatment at $1\;{\mu}g/mL$ low concentration in both mice. In addition, ACR treatment resulted in decreased LPS-induced B lymphocyte proliferation and ConA-induced T lymphocyte proliferation in both groups. However, AsA increased LPS/ConA-induced lymphocyte proliferation in young groups and had no effects in old mice except at $0.5\;{\mu}g/mL$ Thus, the present data indicate that there is no difference effect of ACR and AsA on lymphocyte proliferation, whereas the effect of AsA on mitogen-induced cell proliferation was reduced in old mice. Overall, our results suggest that various immunomodulators have differing effects of lymphocytic proliferation on young versus aged mice.

• 생명과학회지
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• 제17권1호
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• pp.31-38
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• 2007

사람의 장티푸스 연구는 생쥐에 감염되는 Salmonella typhimurium를 모델로 연구되고 있으며, 생쥐에 있어서 S. typhimurium의 감염은 이자세포의 증식반응을 감소시키는 것으로 알려져 있다. S. typhimurium lipid A의 처리가 T세포 mitogen에 의한 이자 세포의 증식에 어떤 영향을 주는 가를 in vitro와 ex vivo조건에서 알아 보았다. Lipid A 단독 처리는 이자 세포의 증식을 보였으나, lipid A 처리 후 T 세포 mitogen인 concanavalin A (Con A)와 phytohemagglutinin (PHA)에 의한 in vitro와 ex vivo 조건에서의 이차 처리는 오히려 세포증식이 억제되었다. Lipid A를 주사한 생쥐로부터 분리한 이자 세포에서 대식세포를 제거하였을 조건에서는 T 세포 mitogen에 의한 증식 효과가 유지되었으나 대식세포를 제거하지 않았을 경우에는 T세포 mitogen에 의한 증식 효과가 억제되었다. Lipid A를 주사한 생쥐에서 얻은 대식세포를 포함한 이자세포의 숫자를 증가하면서 Lipid A를 주사하지 않은 생쥐에서 얻은 이자세포와 혼합 배양하였을 때 Lipid A를 주사한 생쥐에서 얻은 대식세포를 포함한 이자세포의 숫자가 높을수록 Con A와 PHA에 의한 증식억제가 높게 측정되었다. 이러한 결과는 Con A와 PHA의 이자세포 증식 기능이 lipid A의 전처리에 의해 활성화된 대식세포의 직접적인 접촉 작용으로 억제된 것으로 생각된다. 본 연구의 결과를 바탕으로 억제에 관여하는 대식세포 표면분자를 밝히는 것이 사람의 장티푸스 연구에 도움이 되리라 생각된다.

• Archives of Pharmacal Research
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• 제15권4호
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• pp.275-282
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• 1992

The present work was designed to investigate the effects of barzilin on ConAinducedd TCGF release, responsiveness to standardd IL-2, and mitogens-induced proliferation of splenocyte when administered intraperitoneally to 8 week-old C57BL/6 mice for 2 consecutive days. Immunological tests were performed 72 hours after the treatment of brailin. The administration of 50 mg/kg brazilin caused a noticeable increase in TCGF release and responsiveness to standard II-2 but inhibited mitogens-induced proliferation of splenocyte. These results that brazilin is able to modular immunological functions despite of its inhibitory effect on mitogen induced cell proliferation.

• 약학회지
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• 제43권2호
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• pp.208-213
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• 1999

The effects of five lupane-triterpenoids from leaves of two Acanthopanax spp., chiisanogenin, chisanoside and $22{\alpha}-hydroxychiisanogenin$, acakoreoside A and acantrifoside A on the mitogen-induced proliferation were investigated in vitro. T cell proliferation (TCP) to concanavalin A (Con A) and the B cell proliferation (BCP) to lipopolysaccharide (LPS) were increased by chiisanogenin. TCP to Con A was significantly increased by chiisanoside and acankoreoside A, but not affected by chiisanogenin, $22{\alpha}-hydroxychiisanogenin$ and acantrifoside A, BCP to LPS was significantly increased by acankoreoside A and acantrifoside A, and slightly increased by chiisanoside, chiisanogenin and $22{\alpha}-hydroxychiisanogenin$.

• 약학회지
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• 제48권1호
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• pp.41-46
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• 2004

Mancozeb, a polymeric complex of zinc and manganese salts of ethylene bisthiocarbamate (EBDC), is used widely in agriculture as fungicides, insecticides, and herbicides. Mancozeb can be occupationally and environmentally exposed to human and has been reported to induce estrogenic activity, therein it is considered as an endocrine disrupter, We investigated the effects of acute exposure of Mancozeb on the immune function in mice. After single oral administration of Mancozeb to female ICR mice, the immunopathological parameters (body- and organ-weight, splenic cellularity hematological parameters), mitogen (Con A, PHA+IL-2, LPS)-induced splenocyte proliferation (SP) and splenic IgM plaque forming cell (PFC). WBC and splenic cellularity were decreased, but liver-, kidney-, and spleen-weight were increased when compared with control group. Splenic IgM PFC against SRBC was slightly lowered. Mitogen-induced proliferation of spleen cells from Mancozeb-treated mice was not signifcantly changed ex vivo, however, SP in vitro were significantly lowered in concentration dependent manner. These results indicate that Mancozeb could affect the immune function in mice.

• Toxicological Research
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• 제8권2호
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• pp.191-203
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• 1992

The immunosuppressive effects of safrole were studied in female BALB/c mouse. Mice were given 100,200and 400mg safrole/kg daily for 14days and evaluated on day 15. The day 4 immunogloblin-M antibody response to T-dependent antigen, sheep red blood cells (SRBC) was inhibited dose-dependently in all doses studied. In vitro antibody response to polyclonal antigen, lipopolysaccharide (LPS) by spleen cell suspensions from safrole-treated mice were also significantly inhibited. When safrole was treated for 14days to mice, and mitogen-induced proliferation of splenocytes were assayed on day 15, there were significant suppression of responses to B-cell mitogen, LPS and T-cell mitogen concanavalin A(Con A) at a dose of 400mg safrole/kg. Direct addition of safrole on the splenocyte culture also produced a dose dependent suppression on in vitro antibody response to LPS, and mitogen-induced lymphoproliferatin at doses of 100,200,400 and 800${\mu}M$ safrole. The role of metabolic activation in safrole-induced suppression of in vitro antibody response was studied using splenocyte-hepatocyte coculture system. The suppression of in vitro antibody respose to LPS by safrole was not altered when safrole were incubated in the splenocyte-hepatocyte system for 4hr as compared with direct addition of safrole in splenocytes culture. Neither the addition of salicylamide, sulfotransferase inhibitor, nor the addation of inorganic sulfate, sulfation cofactor to the splenocyte-hepatocyte coculture, altered the suppression of antibody response by safrole. These results suggest that the immunosuppression by safrole may not by produced by the reactive metabolites which are mediated in carcinogenesis of safrole.

• 대한의생명과학회지
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• 제12권3호
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• pp.249-254
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• 2006

It has been reported that liver is a very important organ to xenotransplantation. Pig is known to be a most suitable species in transplantation of human organs. However, the physiological function of pig hepatocytes is not clear elucidated. Epidermal growth factor (EGF) is known to be a mitogen in various cell systems. Thus, we examined the effect of EGF on cell proliferation and its related signal cascades in primary cultured pig hepatocytes. EGF stimulates cell proliferation in a dose (>1ng/ml) dependent manner. EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by AG 1478 ($10^{-6}M$, an EGF receptor antagonist) genistein and herbymycin A (tyrosine kinase inhibitors, $10^{-6}M$), suggesting the role of activation and tyrosine phosphorylation of EGF receptor. In addition, EGF-induced increase of $[^3H]-thymidine$ incorporation was prevented by neomycin $(10^{-4}M)$, U73122 $(10^{-5}M)$ (phospholipase C [PLC] inhibitors), staurosporine ($(10^{-8}M)$, or bisindolylmaleimide I $(10^{-6}M)$ (protein kinase C [PKC] inhibitors), suggesting the role of PLC and PKC. Moreover, EGF-induced increase of $[^3H]-thymidine$ incorporation was blocked by PD 98059 (a p44/42 mitogen activated protein kinase [MAPK] inhibitor), SB 203580 (a p38 MAPK inhibitor), and SP 600125 (a JNK inhibitor). EGF increased the translocation of PKC from cytosol to membrane fraction and activated p42/44 MAPK, p38 MAPK and JNK. In conclusion, EGF stimulates cell proliferation via PKC and MAPK in cultured pig hepatocytes.

• Archives of Pharmacal Research
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• 제15권4호
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• pp.283-288
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• 1992

This work was performed to investigate the effects of brazilin in vitro on mitrogen-induced proliferation, ConA-induced TCGF release and responsiveness to recombinant-induced proliferation, ConA-induced TCGF release and responsiveness to recombinant IL-2 using splenocytes from C57BL/6 female mice. Brazilin (29-80 ng/ml) caused a noticeable increase in TCGF production of splenocytes, but did not affect responsivness to recombinant IL-2, the expression of ConA-induced high affinity IL-2 receptor and mitogen-induced proliferation of splenocytes.

• Toxicological Research
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• 제8권1호
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• pp.1-7
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• 1992

Brazilin, the main constitutent of Caesalpinia sappan, was examined for its immunomodulating activities in normal CBA mice. Mitogen induced proliferation and production of ConA induced T-cell growth factors (TCGF) of splenocytes were significantly reduced in brazilin treated group, cmpared to control group. It was also found that suppressor activities of splenocytes in brazilin treated group was significantly increased compared to those in normal control group.

• 대한의생명과학회지
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• 제2권2호
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• pp.175-185
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• 1996

모든 진핵세포에 존재하며 세포의 성장 및 분화에 주로 관계되는 신호전달물질의 하나인 Mitogen-activated protein(MAP)kinase의 mitogen에 의한 핵내 활성화와 기질 인산화에 대해 알아보기 위해 본 실험을 수행하였다. P388세포를 10% fetal bovine serum이 첨가된 DMEM배지에 배양한 후, 혈청이 들어있지 않은 배지에서 24시간 더 배양하고 serum 및 PMA를 농도별로 처리하여 세포성 장을 위한 최적 농도를 확인한 결과 serum은 5-20% 농도에서 세포성장을 촉진시켰고 PMA는 실험한 모든 농도에서 세포성장을 거의 촉진시키지 못하는 경향을 확인하였다. 이어 P388 세포를 serum 및 PMA로 10 분간 활성화하여 파쇄한후 세포질분획과 핵분획으로 분리하여 각 분획을 10% gel 상에서 전기영동 하여 nitrocellulose paper에 옳긴 후 anti-ERKI antibody를 이용해 확인해본 결과 serum, PMA로 처리된 세포 모두에서 MAP kinase의 핵내 이동이 관찰되었으며 특히 세포질 내에 주로 존재하는 42, 44 Kd의 MAP kinase isoform중 42 Kd의 isoform이 주로 핵내로 이동되는 것이 관찰되었다. MAP kinase의 기질인산화 실험을 위해 serum으로 활성화시킨 세포를 파쇄하여 SP-sephadex C-50, Phenyl superose, Mono Q column의 순서로 chromatography를 시 행하여 MAP kinase를 부분분리 하였다. 이와 같이 얻은 MAP kinase를 가지고 면역 T세포에 존재하는 tyrosine kinase인 $p56^{lck}$ 의 N-terminal peptide로 구성된 GST-fusion protein에 대한 인산화를 확인하였다. 또한 세포에서 분리한 MAP kinase를 가지고 transcription factor의 하나인 c-Jun protein에 대한 인산화실험을 실시한 결과 MAP kinase에 의해 인산화 됨이 확인되었다. 이상의 결과를 통해 P388세포는 (1)세포 성장시 외부 신호를 G-protein-coupled receptor/protein kinase C/MAP kinase의 경로보다는 주로 tyrosine kinase receptor protein/Ras/MAP kinase의 경로를 이용하여 핵으로 전달하는 것으로 추측되 며 (2) mitogen의 처리로 활성화된 MAP kinase중 주로 42 Kd isoform이 핵내로 이동하고, 분리한 MAP kinase가 GST-fusion protein과 transcription factor인 c-Jun을 모두 인산화 시키는 결과로 보아 MAP kinase의 isoform에 따라 표적 compartment가 다르고 결과적으로 표적 기질에 차이가 있을지 모른다고 간접적으로 추론할 수 있다.