• Asian-Australasian Journal of Animal Sciences
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• 제18권12호
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• pp.1708-1714
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• 2005

Keratinocyte growth factor (KGF) functions in epithelial growth and differentiation in many tissues and organs. KGF is expressed in the uterine endometrial epithelial cells during the estrous cycle and pregnancy in pigs, and receptors for KGF (KGFR) are expressed by conceptus trophectoderm and endometrial epithelia. KGF has been shown to stimulate the proliferation and differentiation of conceptus trophectoderm. However, the role of KGF on the endometrial epithelial cells has not been determined. Therefore, this study determined the effect of KGF on proliferation and differentiation of endometrial epithelial cells in vitro and in vivo using an immortalized porcine luminal epithelial (pLE) cell line and KGF infusion into the uterine lumen of pigs between Days 9 and 12 of estrous cycle. Results showed that KGF did not stimulate proliferation of uterine endometrial epithelial cells in vitro and in vivo determined by the $^3$H]thymidine incorporation assay and the proliferating cell nuclear antigen staining, respectively. Effects of KGF on expression of several markers for epithelial cell differentiation, including integrin receptor subunits $\alpha$4, $\alpha$5 and $\beta$1, plasmin/trypsin inhibitor, uteroferrin and retinol-binding protein were determined by RT-PCR, Northern and slot blot analyses, and immunohistochemisty, and KGF did not affect epithelial cell differentiation in vitro and in vivo. These results show that KGF does not induce epithelial cell proliferation and differentiation, suggesting that KGF produced by endometrial epithelial cells acts on conceptus trophectoderm in a paracrine manner rather than on endometrial epithelial cells in an autocrine manner.

• Asian-Australasian Journal of Animal Sciences
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• 제16권2호
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• pp.176-179
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• 2003

Insulin-like growth factor-I (IGF-I) is a polypeptide that has the function of regulating the expression of steroid hormones through endocrine, paracrine, and autocrine actions in reproductive organs. Moreover, IGF-I is involved in ovulation, implantation, maintenance of pregnancy, and development of fetuses in animals. Therefore, this study was conducted to investigate the effects of serum IGF-I concentration on progesterone ($P_4$) concentration and pregnancy rates in Korean native cattle (Hanwoo). Blood was collected at estrus (Day 0) and Day 11. Artificial insemination was performed at Day 0. Serum IGF-I and $P_4$ concentrations were measured by radioimmunoassay (RIA). Overall, $P_4$ concentration was higher at Day 11 than Day 0, whereas the pattern of IGF-I concentration was reversed. When animals were divided into two groups depending on the pregnancy status, $P_4$ concentrations of the pregnant group was significantly higher than that of the non-pregnant group at Day 0 (p<0.05) and Day 11 (p<0.05). But, lower IGF-I concentrations were detected in the pregnant group at Day 0 (p<0.05) and Day 11 (p<0.05) compared to the non-pregnant group. In conclusion, these results indicated that serum IGF-I is inversely associated with $P_4$ concentration during early pregnancy in Hanwoo.

• International Journal of Vascular Biomedical Engineering
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• 제2권1호
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• pp.17-24
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• 2004

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (namely multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp, declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.137-142
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• 2011

Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a variety of behavioral and physiological changes in animals. The stomach, as the most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is crucial for the initiation of a full stress response against all harmful stress. Thus, the purpose of this study was to examine whether ELF-MF stimuli induce changes in the activity of neuroendocrine cells, considering their involvement in endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered the distribution and occurrence of gastrin, ghrelin and somatostatinpositive endocrine cells in the stomach of rats. The change, however, in the secretion of those hormones into blood from endocrine cells did not appear significantly with ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week induced an increase in $BaSO_4$ suspension propelling ratio of gastrointestinal tract, indicating that ELF-MF affects gastrointestinal motility. Our study revealed that ELF-MF exposure might influence the activity of endocrine cells, an important element of the intrinsic regulatory system in the digestive tract. The pathophysiological character of these changes and the mechanism responsible for neuroendocrine cell are still unclear and require further studies.

• Journal of Ginseng Research
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• 제41권3호
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• pp.268-276
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• 2017

Background: UV-B-exposed keratinocytes secrete various paracrine factors. Among these factors, basic fibroblast growth factor (bFGF) stimulates the proliferation of melanocytes. Ginsenosides, the major active compounds of ginseng, are known to have broad pharmacological effects. In this study, we examined the antiproliferative effects of ginsenosides on bFGF-induced melanocyte proliferation. Methods: We investigated the inhibitory effects of Korean Red Ginseng and ginsenosides from Panax ginseng on bFGF-induced proliferation of melan-a melanocytes. Results: When melan-a melanocytes were treated with UV-B-irradiated SP-1 keratinocytes media, cell proliferation increased. This increased proliferation of melanocytes decreased with a neutralizing anti-bFGF antibody. To elucidate the effects of ginsenosides on melanocyte proliferation induced by bFGF, we tested 15 types of ginsenoside compounds. Among them, Rh3, Rh1, F1, and CK demonstrated antiproliferative effects on bFGF-induced melanocyte proliferation after 72 h of treatment. bFGF stimulated cell proliferation via extracellular signal-regulated kinase (ERK) activation in various cell types. Western blot analysis found bFGF-induced ERK phosphorylation in melan-a. Treatment with Rh3 inhibited bFGF-induced maximum ERK phosphorylation and F1-delayed maximum ERK phosphorylation, whereas Rh1 and CK had no detectable effects. In addition, cotreatment with Rh3 and F1 significantly suppressed bFGF-induced ERK phosphorylation. Western blot analysis found that bFGF increased microphthalmia-associated transcription factor (MITF) protein levels in melan-a. Treatment with Rh3 or F1 had no detectable effects, whereas cotreatment with Rh3 and F1 inhibited bFGF-induced MITF expression levels more strongly than a single treatment. Conclusion: In summary, we found that ginsenosides Rh3 and F1 have a synergistic antiproliferative effect on bFGF-induced melan-a melanocyte proliferation via the inhibition of ERK-mediated upregulation of MITF.

• Clinical and Experimental Reproductive Medicine
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• 제44권3호
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• pp.119-125
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• 2017

Objective: In vitro culture of preimplantation embryos is improved by grouping embryos together in a drop of media. Individually cultured embryos are deprived of paracrine factors; with this in mind, we investigated whether the addition of a single embryo-secreted factor, interleukin-6 (IL-6), could improve the development of individually cultured embryos. Methods: Mouse embryos were cultured individually in $2{\mu}L$ of G1/G2 media in 5% oxygen and supplemented with a range of doses of recombinant mouse or human IL-6. Results: Mouse IL-6 increased hatching at doses of 0.01 and 10 ng/mL compared to the control (93% and 93% vs. 78%, p< 0.05) and increased the total number of cells at a dose of 0.1 ng/mL compared to the control ($101.95{\pm}3.36$ vs. $91.31{\pm}3.33$, p< 0.05). In contrast, the highest dose of 100 ng/mL reduced the total number of cells ($79.86{\pm}3.29$, p< 0.05). Supplementation with human IL-6 had a different effect, with no change in hatching or total cell numbers, but an increase in the percentage of inner cell mass per embryo at doses of 0.1, 1, and 100 ng/mL compared to the control ($22.9%{\pm}1.1%$, $23.3%{\pm}1.1%$, and $23.1%{\pm}1.1%$ vs. $19.5%{\pm}1.0%$, p< 0.05). Conclusion: These data show that IL-6 improved mouse embryo development when cultured individually in complex media; however, an excess of IL-6 may be detrimental. Additionally, these data indicate that there is some cross-species benefit of human IL-6 for mouse embryos, but possibly through a different mechanism than for mouse IL-6.

• 한국임상수의학회지
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• 제21권4호
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• pp.336-342
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• 2004

돼지 말초혈액 탐식세포(PMN 및 monocyte)의 탐식성에 있어서 CLA 이성체의 탐식증강 효과를 검토하였다. 탐식세포의 탐식석은 fowl cytomery로 분석하였으며 결과는 다음과 같다. 1. CLA 이성체(CLA mixture, 10t-12c CLA, 9c-11t CLA, 9c-11c CLA, 9t-11t CLA)를 직접 첨가하여 배양한 PMN과 PBMC 및 fowl cytometry cytograpy에서 세포크기에 의해 분획한 monocyte-rich fractiondpsms 탐식증강 효과가 없었다. 2. 각각의 CLA 이성체로 배양한 PBMN 배양상층액으로 PBMC의 탐식활성을 측정한 결과 증강효과는 관찰되지 않았다. 3. CLA 이성체로 배양한 PBMC 배양상층액 중 CLA mixture, 10t-12c CLA, 9c-11c CLA 처리군에서는 PMN과 monocyte-rich fraction의 탐식활성에 있어서 현저한 증강효과가 관찰되었다. 그러나, 말초혈액 탐식세포들은 9c-11c CLA와 9t-11t CLA로 배양한 PBMC 배양상층액에 의해서는 증강효과가 나타나지 않았다. 4. CLA 이성체로 배양한 PMN 배양상층액에 있어서는 PMN과 monocyte-rich fraction의 탐식성을 측정한 결과, 어느 경우에도 증강효과는 나타나지 않았다. 이상의 결과로부터 CLA 중 CLA mixture, 10t-12c CLA. 9c-11t CLA가 돼지 말초혈액 탐식세포에 대하여 탐식증강효과를 가지고 있으며 이러한 증강효과는 직접적이라기보다는 CLA에 의해 활성화된 단핵구세포에서 분비되는 탐식촉진인자를 함유한 가용성 물질에 의해 autocrine 또는 paracrine 양상으로 탐식세포에 작용하는 것으로 생각되었다.

• 한국동물학회지
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• 제39권3호
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• pp.317-324
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• 1996

파골세포는 골조직을 분해하는 세포로 알려져 있다. 따라서, 파골세포 활성조절은 골조직의 성장과 재조합의 조절에 있어 매우 중요한 의미를 갖는다. 기관배양을 통해 파골세포의 활성을 조절하는 여러가지 인자들이 알려져 있다. 그 중에서 transforming growth factor-$\beta$ (TGF-$\beta$)는 골조직 대사에 중요한 영향을 미치는 것이 알려져 있고, 또한 골조직내에 다량 존재하고 있기 때문에, TGF-$\beta$의 파골세포에 대한 효과를 알아보는 것은 전체 파골작용의 조절기작을 알아보는데 있어 중요한 의미를 갖는다. 본 연구인들은 계배를 이용한 파골세포의 배양법을 개발하였고, 이를 파골세포 활성을 측정하는데 사용하였다. 이 방법을 통해, TGF-$\beta$1이 파골세포의 골분해 활성을 증가시킨다는 것을 알수 있었다. 또한, 이러한 활성작용은 TGF-$\beta$의 파골세포에 대한 직접적인 효과라기 보다는 다른 세포를 통한 간접적인 효과일 가능성이 높다는 사실을 알 수 있었다. TGF-$\beta$에 의한 파골세포의 활성화는 nordihydroguaiaretic acid에 의해 현저하게 저해된 반면, idomethacin에 의해서는 저해되지 않았다. 이러한 실험결과들은 TGF-$\beta$가 arachidonic acid의 lipoxygenase 유도체를 통해 파골세포의 영향을 미칠 가능성을 제시하고 있다.

• Journal of Periodontal and Implant Science
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• 제25권3호
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• pp.635-647
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• 1995

Human polymorphonuclear leukocytes(PMN) constitute a first line of defense against all forms of injury and microbial challenge, which share a common cell lineage with macrophage. Microbial component LPS activates macrophages to produce IL-1, MIP-1${\alpha}$, -1${\beta}$, TNF-${\alpha}$ and IL-6, etc. Those cytokines have autocrine function to the macrophages, and paracrine function to other cell such as PMN and affect them to produce some biological functions. Having a responsive homogeneous cell line, HL-60, offers us the possibility of studying extensively on the function of PMN, which were not possible previously with peripheral PMN, due to the short-lived nature and difficulty of getting a purified PMN. In the present study, I performed MIP-1 receptor binding assay using HL-60 cell and human peripheral PMN. Also, in vitro antimicrobial assay was performed using differentiated or undifferentiated HL-60 cell. Differentiation was induced by treatment with 500 M of $N^6,O^2-dibutyryl$ adenosine 3'5' cyclic monophosphate(dbcAMP) (PMN-like cell), or 20ng/ml of 12-O-tetradecanoylphorbol-13-acetate(TPA) (macrophage/monocyte-like cell). Receptors for MIP-1${\alpha}$ were identified on dbcAMP-treated HL-60 as well as peripheral PMN. However, bound radioactive MIP-1${\alpha}$ on differentiated HL-60 was much higher than that of peripheral PMN, which suggest receptor number of differentiated HL-60 cell is higher than that of peripheral PMN. Although both of TPA and dbcAMP treatment significantly enhanced antimicrobial action of HL-60 cell, dbcAMP-treated cell(PMN-like HL-60) killed S.aureus more effectively in this experiment. TPA or dbcAMP treatment significantly enhanced antimicrobial action of undifferentiated HL-60 cell. MIP-1${\alpha}$ further increased enhancing effect of TPA or dbcAMP. IL-1${\alpha}$, however, increased only dbcAMP-induced enhancing effect of antimicrobial action of HL-60 cell. These results suggest that differentiated HL-60 cell could replace peripheral PMN in analysis of various biological functions of cytokines on PMN cell.

• Journal of Periodontal and Implant Science
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• 제25권2호
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• pp.267-278
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• 1995

Human polymorphonuclear leukocytes(PMN) are the most numerous host cell in periodontal pockets and their presumed role is to form a protective barrier between the bacteria and periodontal tissues. Microbial component LPS activates macrophages to produce $IL-1{\beta}$, $MIP-1{\alpha}$, $-1{\beta}$, $TNF-{\alpha}$ and IL-6, etc. These cytokines have autocrine function to the macrophages, and paracrine function to other cell such as PMN and affect them to produce some biological functions. In the present study, human PMN were tested for the expression of $IL-1{\beta}$ and $MIP-1{\alpha}$ mRNA. Also we performed the receptor binding assay and in vitro assay for the antimicrobial action of HL-60 cell to determine whether HL-60 can replace the peripheral PMN in analyzing the biological functions. PMN were stimulated with $IL-1{\beta}$, TPA, $MIP-1{\alpha}$, LPS, IL-2 and total cytoplasmic RNA were extracted for the northern blot analysis. In order to determine the induction kinetics of $IL-1{\beta}$ or $MIP-1{\alpha}$ mRNA expression, cells were stimulated for 0,1,2,3 hours. We found peak expression of $IL-1{\beta}$ mRNA after 1hr of induction with $IL-1{\beta}$, LPS and after 2hr of induction with TPA. $MIP-l{\alpha}$ also induced but a scarce $IL-l{\beta}$ message from PMN. In contrast to the $IL-l{\beta}$ mRNA expression, $MIP-1{\alpha}$ were not induced from PMN in any culture conditions. Receptors for $MIP-1{\alpha}$ were identified on dibutyryl cyclic AMP(dbcAMP)-treated HL-60 as well as peripheral PMN. dbcAMP treatment significantly enhanced antimicrobial action of undifferentiated HL-60 cell. MIP-1 further increased enhancing effect of dbcAMP. $IL-1{\beta}$, to a lesser extent, also increased dbcAMP-induced enhancing effect of antimicrobial action of HL-60 cell.