• Clinical and Experimental Reproductive Medicine
• /
• v.24 no.3
• /
• pp.399-405
• /
• 1997

Progesterone is necessary for successful pregnancy and had immunosuppressive properties. Peripheral blood mononuclear cells (PBMC) from many women with unexplained recurrent spontaneous abortion responded to trophoblast extract in vitro by prolifertion and releasing soluble, heat-labile factors that are toxic to mouse embryos (embryotoxic factors). Accumulating evidence suggests that T Helper (Th)-1 type immunity to trophoblast is correlated with embryotoxic factor production and is associated with pregnancy loss, while Th2-type immunity is associated with successful gestation. The objective of this study was to determine whether progesterone can inhibit Th1-type cytokine secretion (IFN-${\gamma}$, TNF-${\alpha}$) by trophoblast-activated peripheral blood mononuclear cells from 23 nonpregnant women (age 25-35) with unexplained recurrent abortion (median 5, range 3 to 15)who otherwise produce embryotoxic factors in response to trophoblast. We also determined whether progesterone affected Th2-type cytokines (IL-4, IL-10) in this system in vitro and if IL-10 (1,500 pg/mL) could inhibit Th1-type immunity to trophoblast. IFN-${\gamma}$ was detected in 17 of 23 (74%) trophoblast stimulated PBMC culture supernatants ($77.94{\pm}23.79$ pg/mL) containing embryotoxic activity. TNF-${\alpha}$ was detected in 19 (83%) of these same supernatants ($703.15{\pm}131.36$ pg/mL). In contrast, none of the supernatants contained detectable levels of IL-4 or IL-10. Progesterone ($10^{-5}$, $10^{-7}$, $10^{-9}$M) inhibited Th1-type immunity in a dose dependent manner, but had no effect on Th2-type cytokine secretion. The inhibitory effects of progesterone were abrogated with RU486, but did not affect Th2-type cytokine secretion in trophoblast-activated cell cultures. IL-10, like progesterone also inhibited Th1-type cytokine secretion but had no effect on Th2-type cytokines. These data suggest that therapies designed to suppress Th1-type cytokine secretion in women with recurrent abortion who have evidence of Th1-type immunity to trophoblast may be efficacious in preventing pregnancy loss and should be tested in appropriately designed clinical trials.

• Food Science and Preservation
• /
• v.23 no.7
• /
• pp.1026-1032
• /
• 2016

Citrus platymamma hort. ex Tanaka is widely used in traditional Korean medicine because of its medicinal benefits including an anti-inflammatory effect. This study aimed to evaluate changes in the flavonoid content and anti-inflammatory activities of C. platymamma during its harvest period. Fruit peel samples were obtained between September 2015 and February 2016. The results indicate that C. platymamma peel extract (CPE) was an effective inhibitor of lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells. The inhibitory effects of CPE at $100{\mu}g/mL$ concentration included dose-dependent decreases in the expression of iNOS and COX-2 proteins. In addition, CPE decreased the expression of pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. The highest anti-inflammatory activity and flavonoid content were observed in CPE of C. platymamma peel harvested during the immature fruit period in September. Further, to assess the suitability of CPE for cosmetic use, we performed MTT assays using HaCaT keratinocytes and observed that CPE did not exhibit any cytotoxicity. To test the potential application of CPE as a cosmetic material, we also performed primary skin irritation tests on normal skin of 30 volunteers and no adverse reactions were observed. The results of this study indicate that CPE may be considered as an anti-inflammatory candidate for inclusion in cosmetic materials.

• YAKHAK HOEJI
• /
• v.44 no.4
• /
• pp.340-346
• /
• 2000

Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, named as Somatid, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Somatid inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, CaSki) and HaCaT keratinocytes in a dose response manner, In vitro binding assay and ELISA showed that Somatid inhibited the in vitro biding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Somatid inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by Somatid. Our data suggested that Somatid inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas caused by HPV.

• Journal of Life Science
• /
• v.13 no.3
• /
• pp.359-364
• /
• 2003

The seaweed Porphyra pseudolinearis as a dominant species grows at upper of the intertidal zone of the East Sea from October to March. Vegetative cells have not matured during October when observed with naked eye and microscope. In the middle of November, although it didn't distingush between female and male gametophytes by eye, it showed antheridium and carpogonium when observed vertical section under microscope. From early December, It could be distinguished female and male gametophytes clearly. From Feburary it showed shorted length of thalli by release of spermatangia and carposporangia as maturation. At early March, the colar has been decaeded and side of thalli has been melted, completed of release of spermatia. At the end of December, the average length and width of female thalli were 149.9$\pm$5.6mm and 22.2$\pm$2.3mm, respectively. The length and width of male thalli were 149.9$\pm$9.4mm and 20.7$\pm$1.8mm. At the end of January, the average length and width of female thalli were 94.6$\pm$6.4mm and 29.1mm$\pm$5.1, respcetively. The length and width of male thalli were 107.8$\pm$7.3mm and 25.9$\pm$0.9mm. From this period lengths of female and male thalli have already been shortned by the release of spermatia and carpogonia.

• Molecules and Cells
• /
• v.37 no.5
• /
• pp.426-434
• /
• 2014

Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a $Ca^{2+}$-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease. To investigate the role of PADI2 in apoptosis, we generated a Jurkat cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter, and used a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin to activate Jurkat cells. We found that PADI2 overexpression reduced the cell viability of activated Jurkat cells in1a dose- and time-dependent manner. The PADI2-overexpressed and -activated Jurkat cells presented typical manifestations of apoptosis, and exhibited greater levels of citrullinated proteins, including citrullinated vimentin. Vimentin overexpression rescued a portion of the cells from apoptosis. In conclusion, PADI2 overexpression induces apoptosis in activated Jurkat cells. Vimentin is involved in PADI2-induced apoptosis. Moreover, PADI2-overexpressed Jurkat cells secreted greater levels of vimentin after activation, and expressed more vimentin on their cell surfaces when undergoing apoptosis. Through artificially highlighting PADI2 and vimentin, we demonstrated that PADI2 and vimentin participate in the apoptotic mechanisms of activated T lymphocytes. The secretion and surface expression of vimentin are possible ways of autoantigen presentation to the immune system.

• Molecules and Cells
• /
• v.37 no.11
• /
• pp.833-840
• /
• 2014

Cullin4-RING ubiquitin ligase (CRL4) is a family of multi-subunit E3 ligases. To investigate the possible involvement of CRL4 in heat stress response, we screened T-DNA insertion mutants of putative CRL4 substrate receptors that exhibited altered patterns in response to heat stress. One of the mutants exhibited heat stress tolerance and was named heat stress tolerant DWD1 (htd1). Introduction of HTD1 gene into htd1-1 led to recovery of heat sensitivity to the wild type level, confirming that the decrease of HTD1 transcripts resulted in heat tolerance. Therefore, HTD1 plays a negative role in thermotolerance in Arabidopsis. Additionally, HTD1 directly interacted with DDB1a in yeast two-hybrid assays and associated with DDB1b in vivo, supporting that it could be a part of a CRL4 complex. Various heat-inducible genes such as HSP14.7, HSP21, At2g03020 and WRKY28 were hyper-induced in htd1-1, indicating that HTD1 could function as a negative regulator for the expression of such genes and that these genes might contribute to thermotolerance of htd1-1, at least in part. HTD1 was associated with HSP90-1, a crucial regulator of thermotolerance, in vivo, even though the decrease of HTD1 did not affect the accumulation pattern of HSP90-1 in Arabidopsis. These findings indicate that a negative role of HTD1 in thermotolerance might be achieved through its association with HSP90-1, possibly by disturbing the action of HSP90-1, not by the degradation of HSP90-1. This study will serve as an important step toward understanding of the functional connection between CRL4-mediated processes and plant heat stress signaling.

• Molecules and Cells
• /
• v.41 no.7
• /
• pp.653-664
• /
• 2018

The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

• Archives of Plastic Surgery
• /
• v.37 no.4
• /
• pp.323-328
• /
• 2010

Purpose: Adipose-derived stromal cells (ADSCs) are multipotent cells that have been found to promote wound healing through the process of angiogenesis and reepithelialization. Generally, it is well known that the antigenicity of ADSCs doesn't affect stem cell therapy. In this study, we investigated the effect of allogeneic ADSCs in the wound healing process by applying allogeneic ADSCs on the wound healing splint model of mice. Methods: Adipose tissue was harvested from the epididymal fat pads of BALB/c and C57BL/6 mice. Twenty four mice BALB/c were divided into three groups; control, isogeneic, and allogeneic groups. Two full thickness defects with 6 mm diameters were created on the back of BALB/c mice. $1{\times}10^6$ ADSCs from BALB/c mice were applied on the isogeneic group. In the allogeneic group, ADSCs from the C57BL/6 mice were applied. No cells were applied to the control group. The sizes of the wounds were evaluated in 3, 5, 7, 10, and 14 days after the wounds were applied, and tissues were harvested in 7 and 14 days for histological analysis. Results: Wound healing rates had showed significant increase in 10, and 14 days when the isogeneic group was compared to the control group, but the allogeneic group showed significantly decrease compared to the isogeneic group (p<0.05). Histological scores in the isogeneic group were significantly high, but significantly lower in the allogeneic group when compared to the isogeneic group in 2 weeks (p<0.05). In the isogeneic group, thick inflammatory cell infiltration with abundant capillaries were observed in 1 week, and thick epithelium with many large capillaries were observed in 2 weeks. Conclusion: When isogeneic ADSCs were applied to wounds, they presented a faster wound healing rate compared to controls and the allogeneic group. Unlike general stem cell therapy, these findings suggest that cell therapy targeted at enhancing wound healing may benefit from the use of ADSCs with identical antigenicity, as opposed to allogeneic or xenogenic ADSCs.

• Korean Journal of Microbiology
• /
• v.47 no.4
• /
• pp.295-301
• /
• 2011

Aquaporin is a water channel protein, which is classified as Major Intrinsic Protein (MIP), found in almost all organisms from bacteria to human. To date, more than 200 members of this family were identified. There are two major categories of MIP channels, orthodox aquaporins and aquaglyceroporins, which facilitate the diffusion across biological membranes of water or glycerol and other uncharged compounds, respectively. The full genome sequencing of various fungal species revealed 3 to 5 aquaporins in their genome. Although some functions of aquaporins found in yeast were characterized, however, no functional characteristics were studied so far in filamentous fungi, including Aspergillus sp. In this study, one orthodox aquaporin homolog gene, aqpA, and four aquaglyceroporin homologs, aqpB-E, in a model filamentous fungus Aspergillus nidulans were identified and the function of the aqpA gene was characterized. Knock-out of the aqpA gene didn't show any obvious phenotypic change under the osmotic stress, indicating that the function of the gene does not involved in the osmotic stress response or the function could be redundant. However, the mutant showed antifungal susceptibility resistance phenotype, suggesting that the function of the aqpA gene could be involved in sensing the antifungal substances rather than the osmotic stress response.

• Molecules and Cells
• /
• v.39 no.7
• /
• pp.557-565
• /
• 2016

The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory $PILR{\alpha}$ and activating $PILR{\beta}$ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit ${\beta}1$ integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of ${\beta}1$ integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of ${\beta}1$ integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.