• Parasites, Hosts and Diseases
• /
• v.62 no.3
• /
• pp.270-280
• /
• 2024

Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B₄ (LTB₄) and various cysteinyl leukotrienes (CysLTs) which included LTC₄, LTD₄, and LTE₄. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47^phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47^phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.

• Clinical and Experimental Pediatrics
• /
• v.49 no.9
• /
• pp.977-982
• /
• 2006

Purpose : There has been an increasing amount of literature concerning the association between Mycoplasma pneumoniae and asthma pathogenesis. Interleukin(IL)-6 stimulates the differentiation of monocytes, and can promote Th2 differentiation and simultaneously inhibit Th1 polarization. IL-8 is a potent chemoattractant and, it has been suggested, has a role in asthma pathogenesis. Nitric oxide (NO) synthesized by airway epithelium may be important in the regulation of airway inflammation and reactivity. Vascular endothelial growth factor(VEGF) has been reported to be a mediator of airway remodeling in asthma. We investigated the effects of M. pneumoniae on IL-6, IL-8, NO and VEGF production in human respiratory epithelial cells. Methods : A549 cells were cultured and inoculated with M. pneumoniae at a dose of 20 cfu/cell. After infection, the presence of M. pneumoniae in epithelial cell cultures was monitored by immunofluorescence and confirmed by polymerase chain reaction(PCR) detection. IL-6, IL-8 and VEGF were determined by an enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. NO was measured using the standard Griess reaction. Results : In A549 cells, M. pneumoniaeinduced IL-6, IL-8, NO and VEGF release in time-dependent manners. It also induced mRNA expression of IL-6, IL-8 and VEGF in similar manners. Conclusion : These observations suggest that M. pneumoniae might have a role in the pathogenesis of the allergic inflammation of bronchial asthma.

• Reproductive and Developmental Biology
• /
• v.28 no.3
• /
• pp.203-207
• /
• 2004

The transgenic mice carrying human Interleukin-10 (hIL-10) gene in conjunction with bovine (3 -casein promoter express hIL-10 in milk during lactation. In this study, stability of germ line transmission and expression of hIL-10 transgene integrated into host chromosome were monitored up to generation F8 of transgenic mice. When male mouse of generation F8 was crossbred with normal females, approximately half of offspring (50.9±5.8%) were identified as transgenic mice. Generation F9 to F15 mice also showed similar transmission rates (66.0±20.1%, 61.5±16.7%, 41.1±8.4%, 40.7±20.3%, 61.3±10.8%, 49.2±18.8% and 43.8±25.9%, respectively), implying that hIL-10 transgene can be transmitted stably up to long term generation in the transgenic mice. Expression levels of human IL-10 from milk of generation F9 to F14 mice were 3.6± 1.2 mg/ml, 4.2±0.9 mg/ml, 5.7±1.5 mg/ml, 6.3±3.5 mg/ml, 6.8±4.5 mg/ml and 6.8±3.1 mg/ml, respectively, which was showed high-level expression compared with that of generation F1 (1.6 mg/ml) mice. In conclusion, our results suggest that transgenic mice can be continuously passed their transgenes to the progeny through the breeding program with the same productivity of human IL-10 protein in their milk.

• Journal of Microbiology and Biotechnology
• /
• v.30 no.12
• /
• pp.1810-1818
• /
• 2020

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against pro-inflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL-17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.

• Journal of Sasang Constitutional Medicine
• /
• v.21 no.1
• /
• pp.139-149
• /
• 2009

1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{\kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${\alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${\alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{\kappa}B$ through inhibition of the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is an inhibitor of $NF{\kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{\kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

• Korean Journal of Pharmacognosy
• /
• v.34 no.3 s.134
• /
• pp.228-232
• /
• 2003

For effective management of atopic dermatitis, it is important to introduce a therapeutic agent although having the fewest side effects, has the greatest anti- inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM composed of several plant extracts. This study was designed to investigate anti-inflammatory and immunomodulatory effects of BSASM. As a first step, $NF-{\kappa}B$ luciferase reporter assay was performed to know the involvement of BSASM in the production of proinflammatory cytokines because $NF-{\kappa}B$ element has been known to play a major role in expression of cytokine genes such as interleukin-8 (IL-8) or tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. LPS (lipolysaccharide)-induced $NF-{\kappa}B$ activation was inhibited by BSASM. In addition, we found the fact that BSASM inhibits LPS-induced produced production of IL-8 and $TNF-{\alpha}$ proinflammatory cytokines, indicating BSASM has anti-inflammatory effect. In interleukin-2 (IL-2) luciferase reporter assay in Jurkat T cells, BSASM reduced PHA (Phytohemagglutinin)-induced IL-2 luciferase activity, suggesting the possibility that BSASM might also have an immunomodulatory function in T cell-mediated immune response. Based on these results, we suggest the possibility that BSASM can be introduced to improve symptom of immune-related skin diseases, namely, atopic dermatitis.

• Journal of Microbiology and Biotechnology
• /
• v.16 no.7
• /
• pp.1078-1083
• /
• 2006

Capsaicin is the active ingredient in chili pepper and has an inhibitory effect on Helicobacter pylori growth and $NF-{\kappa}B$ activation. The present study examined the effect of capsaicin on interleukin (IL)-8 production by H. pylori ATCC 43504-infected MKN-45 cells, a gastric epithelial cell line. The viability of the MKN-45 cells treated with capsaicin at 0, 50, 100, 250, and $500\;{\mu}M$ was 99, 98, 99, 99, and 85%, respectively. A capsaicin concentration as low as $50\;{\mu}M$ significantly inhibited the IL-8 production induced by H. pylori ATCC 43504 infection (43.2% of control) during 24 h of incubation. However, low concentrations of capsaicin $(50\;and\;100{\mu}M)$ did not significantly inhibit the IL-8 production by $TNF-{\alpha}-$ or PMA-treated MKN-45 cells. Therefore, the overall inhibitory effect of capsaicin on H. pylori ATCC 43504 was the sum of H. pylori ATCC 43504 growth inhibition, host cell survival, and $NF-{\kappa}B$ signal cascade inhibition.

• Restorative Dentistry and Endodontics
• /
• v.27 no.1
• /
• pp.1-11
• /
• 2002

Immune responses associated with bacterial infection involve various inflammatory cells. Clinical symptoms and pathologic features are particularly influenced by the predominant cells Among inflammatory cells, T cells have the heterogenity. T cells may develop into the mature cells expressing the cell surface markers with different functions and T helper cells are categorized into Th1 and Th2 cells based on their different patterns of cytokine production. The objective of this study was to investigate the change of expression of surface markers on T cells and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. We experimentally induced pulpal inflammation in rat incisors by drilling without coolant and innoculated with Streptococcus mutans (S.M. group), Porphyromonas endodontalis (P.E. group), or only sterile cotton (control group). After 1, 2, and 5 days, mandibular incisors were extracted and the pulp tissues were extirpated The expressions of IL-2 recepters (CD25) and ICAM-1 (CD54) on CD4+ and CD8+ cells in the pulps were determined using a flow cytometer, and the concentration of IL-2, IFN-$\gamma$ and IL-4 was measured by enzyme-linked immunosorbent assay. The results were as follows: 1 In the S.M. group, CD4+ cells were more increased at 2nd day than 1st day and in the P.E. group, CD8+ cells were more increased at 2nd day than 1st day. 2. The percentages of CD4+, CD4+25+ and CD4+54+ cells were decreased in the pulp tissues at 5th day after irritation in all groups. 3. The ratios of CD4+/CD8+, CD4+/CD4+25+ and CD4+/CD4+54+ in the pulps at 2nd day after irritation by P. endodontalis were significantly lower than the other groups. 4. The higher concentrations of IFN-$\gamma$ than IL-4 in the pulps at 2nd day after irritation by P. endodontalis showed that T helper 1 reaction were predominant in the early stage of the pulpal inflammation induced by P. endodontalis. 5. The higher concentrations of IL-4 than IFN-$\gamma$ in the pulps at 1st day and 5th day after irritation by S. mutans were measured but the differences were not significant.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.213-220
• /
• 2023

The most common skin disease, acne, often occurs in adolescence, but it is also detected/observed in adults due to air pollution and drug abuse. One of the causative agents of acne, Cutibacterium acnes (C. acnes) plays a role in the development of skin acne by inducing inflammatory mediators. Torreya nucifera (TN) is an evergreen tree of the family Taxaceae, having well reported antioxidant, anti-proliferative, liver protection, and nerve protection properties. Improvement of these bioactive properties of natural products is one of the purposes of natural product chemistry and pharmaceuticals. We believe biorenovation could be one improvement strategy that utilizes microbial metabolism to produce unique derivatives having enhanced bioactivity. Therefore, in this study, the C. acnes-induced RAW264.7 inflammation model was used to evaluate the anti-inflammatory activity of the biorenovated Torreya nucifera product (TNB). The results showed improved viability of TNB-treated cells compared to TN-treated cells in the concentration range of 50, 100, and 200 ㎍/mL. At non-toxic concentrations, TNB inhibited the production of nitric oxide and prostaglandin E2 by suppression of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. TNB also attenuated the expression of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α induced by C. acnes. Furthermore, TNB inhibited the nuclear factor-κB signaling pathway, a transcription factor known to regulate inflammatory mediators. Based on these results, this study suggests the potential of using TNB as natural material for the treatment of acnes and thus, supporting our postulation of biorenovation as an bioactivity improvement strategy.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.19 no.1
• /
• pp.47-68
• /
• 2006

Purpose : This study was carried out to investigate the effects of Gagamdokhwalgisang-Tang on the morphometric changes of femur, and on the hormones and cytokines associated with bone metabolism in overiectomized rats. Methods : Twenty-four female Sprague-Dawley rats were divided into sham operated group(normal) ovariectomized group(control), and treated with extract of GD group(treated). Each group was evaluated the changes of body weight at 0, 3, 6, 8 weeks after ovariectomy. Morphometric analysis(femur weight, femur/body weight ratio, femur ash weight femur ash/body weight ratio cross sectional area of compact bone and concellous bone of femur) and histopathological examination were performed at 8 weeks after ovariectomy. Estrogen, Alkaline Phosphatase(ALP) and cytokine(Tumor necrosis $factor-{\alpha}$, $Interleukin-l{\beta}$, Inerleukin-6) assay were performed at 8 weeks after ovariectomy. Results : 1. The body weight of control and treated group was significantly increased(p<<0.001) compared with the normal group at 8 weeks. 2. The femur weight and femur/body weight ratio of treated group were significantly increased(p<<0.05, p<<0.01) compared with the control group at 8 weeks. 3. The femur ash weight showed no significantly different changes, but femur ash/body weight ratio of treated group was significantly increased(p<<0.05) compared with the control group at 8 weeks. 4. In the cross sectional area of cancellous bone of femoral body, the treated group was significantly increased(p<<0.001) compared with the control group at 8 weeks. 5. The serum estrogen level of treated group showed no significantly different changes compared with the control group at 8 weeks. 6. The serum ALP activity of treated group was significantly decreased(p<<0.01) compared with the control group at 8 weeks. 7. The serum Tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ level of treated group was significantly decreased(p<<0.05) compared with the control group at 8 weeks. 8. The serum $Interleukin-l{\beta}(IL-1{\beta})$ level of treated group was significantly decreased(n<<0.001) compared with the control group at 8 weeks. 9. The serum Interleukin-6(IL-6) level of treated group was significantly decreased(P<<0.01)compared with the control group at 8 weeks. Conclusion : These results indicate that GD inhibits bone resorption in ovariectomized rats. And the major inhibitory mechanism may be related to the inhibitory effects of GD on the secretion of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 in the pathogenesis of osteoporosis in estrogen deficient rats.