• IMMUNE NETWORK
• /
• 제21권3호
• /
• pp.18.1-18.13
• /
• 2021

TLR signaling is critical for broad scale immune recognition of pathogens and/or danger molecules. TLRs are particularly important for the activation and the maturation of cells comprising the innate immune response. In recent years it has become apparent that several different TLRs regulate the function of lymphocytes as well, albeit to a lesser degree compared to innate immunity. TLR2 heterodimerizes with either TLR1 or TLR6 to broadly recognize bacterial lipopeptides as well as several danger-associated molecular patterns. In general, TLR2 signaling promotes immune cell activation leading to tissue inflammation, which is advantageous for combating an infection. Conversely, inappropriate or dysfunctional TLR2 signaling leading to an overactive inflammatory response could be detrimental during sterile inflammation and autoimmune disease. This review will highlight and discuss recent research advances linking TLR2 engagement to autoimmune inflammation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제27권5호
• /
• pp.385-396
• /
• 2001

The purpose of this experiment was to examine the histological changes and the pattern of expression of proliferating cell nuclear antigen(PCNA) and type I collagen in the elongated bone affected by osteodistraction of the mandibular body in an adult canine model. Seven adult male mongrel dogs weighing over 20kg were used for this experiment. The author excluded 3 animals because they died before the planned time of sacrifice. The custom-made linear extraoral device and 4 bicortical fixation screws 2.3mm in diameter, 50mm in total length, 15mm in screw length were used in each animal. The distal part of the distractor produced a 0.75mm gap between proximal and distal bony segments every $360^{\circ}$ turn of the rotation rod of the device. The mandibular body of the right side from each animal was experimental side and the left side was left intact and served as control. At the experimental side, the mandibular body was osteotomized. After 5-day latency period, the segments were distracted with a rate of 1.1mm/day and a rhythm of two/day for ensuing 7 days. The animals were sacrificed at the 4th. 17th, and 32th day after the end of the distraction. The bony specimens were decalcified, embedded in paraffin, sectioned $5{\mu}m$ thick and stained with Masson trichrome and examined under the light microscope. The immunohistochemical examinations using anti-PCNA antibody and anti-type-I collagen antibody were performed to examine the pattern of the expression of PCNA and type I collagen, respectively. Results : 1. The mean increment of the distance between the proximal and distal screw-holding parts of the distractor was 6.8mm. The average elongation of the mandible in the experimental side was 5.3mm. The loss of elongation was 1.5mm in average. 2. New bone was already observed at the 4th. day after the end of distraction. But, bony union was not completed in the distraction gap at the 32th. day after the end of distraction by radiographic and microscopic examinations. 3. The expression rate of PCNA positive cells in the distraction gap had a tendency of decrease from 35.1-68.8% initially, to 49.1%, and finally to 17.6-27.2%. But at the final period, the tissue of the elongated gap still had the ability of cell proliferation. On the other hand, the expression of PCNA positive cells in the control side were negligible through the experimental period. 4. PCNA positive cells were observed primarily both at the central fibrous zone and at the region of just adjacent to CFZ which initiated new bone formation. 5. The expression pattern of the type I collagen was not zone-specific. They were observed diffusely throughout the elongation gap. 6. The predominant mechanism of new bone formation in the distraction gap was intramembranous. But, some of the regenerated bone was formed by endochondral ossification.

• 환경생물
• /
• 제17권4호
• /
• pp.481-492
• /
• 1999

득량만 식물플랑크톤 군집의 시.공간적 분포특성을 파악하기 위해 1992년 6월부터 1993년 4월까지 만내 38개의 관측점을 대상으로 월별 조사를 실시하였다. 결과, 득량만에서 출현이 확인된 식물플랑크톤 종은 식물성 편모조류 33종을 포함 50속 75종이 동정되었다. 계절별로는 여름과 가을에 비교적 다양한 종이 출현을 보이고 있는 반면, 봄과 겨울에 단순한 종 출현 특성을 나타내었다. 우점종은 연간 규조류에 의해 지배되고 있으며, 여름에 P. alata, G. flaccida, S. costatum, L. danicus와 Pn. longissima, 가을에 St. pulmeriana, Ch. curvisetus와 B. puxillifera, 겨울에 S. costatum, Ch. curvisetus, E. zodiacus와 Pn. pungens, 그리고 봄에 As. glacialis, As. kariana, N. pelagica, Th. nitzschioides.와 S. costatun에 의해 우점되어, 비교적 계절적으로 뚜렷한 우점종 천이가 보여졌다. 식물플랑크톤 현존량은 2.6$\times$$10^3$cells/1에서 $1.0{\times}10^6cells/l$의 범위로 변동하고 있으며, 저수온기에 높고, 고수온기에 낮은 특성을 나타내고 있었다. 그리고 공간적 분포 차는 해역에 따라 수온 차가 심한 여름과 겨울에 매우 크게 나타나고 있었으며, 해역 특성에 의해 단기적인 변동 특성을 나타내고 있었다. 다만, 최고 높은 현존량은 S. costatum의 1종에 의해 지배되고 있다. Chlorophyll $\alpha$농도는 0.19$\mu$g/1에서 12.3$\mu$g/1범위로 변동하여, 8월, 9월 및 3월에 높고, 7월에 낮은 값을 나타내었다. 그리고, 뚜렷한 계절적 변화양상은 보이지 않고 있으며, 해역별로 큰 차를 나타내, 시간적인 농도 차보다 공간적 분포 차가 더욱 크고, 저층이 표층보다 높은 생물량을 나타내는 특성을 보였다. 또한, 만 중앙부인 득량도 인근해역에서는 해수유동 결과 형성되고 있는 것으로 판단되는 고농도의 소규모적인 불균일 분포 특성도 강하게 나타났다. 해역적으로는 수심의 얕은 북서 연안해역에서 비교적 높은 생물량을 나타내고 있는 반면, 고흥반도 연안과 수로부 등 비교적 수심이 깊은 만의 동남 해역에서 낮은 생물량을 나타내고 있는 특성으로 연중 높은 생물량을 나타내고 있어, 득량만은 식물플랑크톤에 의한 높은 생물생산이 연중 유지되고 있는 해역으로 판단되었다.

• Toxicological Research
• /
• 제17권2호
• /
• pp.73-82
• /
• 2001

The incidence and distribution of necrotic and apoptotic neural cells, and activated astrocytes in the brain of rats intoxicated intra peritoneally with diisopropylfluorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg) were pretreated intramuscularly 30 min and 10 min, respectively, prior to diisopropylfluorophosphate (4-10 mg/kg) administration. Diisopropylfluorophosphate induced severe limbic seizures, early necrotic and delayed apoptotic brain injuries, and rapid astrocytic responses. The necrosis, which was closely related to seizure intensity, was observed as early as 1 hr after intoxication predominently in hippocampal pyramidal cells, cerebellar Purkinje cells and neurons in pyriform/entorhinal cortices, showing malacia of neurophils. In contrast, apoptosis started to appear 12 hr after intoxication in neurons in thalamus, amygdala and neocortex, and ephendymal cells surrounding the 4th ventricle. Since marked apoptosis was induced in rats exhibiting relatively-low seizure intensity, the degree of necrosis and apoptosis was shifted to each type of injury according to the seizure intensity. Activated astrocytes, observed within 1 hr along the limbic system, were suggested to affect the neural injury patterns by producing high level of nitric oxide. However, the distribution of activated astrocytes was not in parallel with those of necrotic or apoptotic injuries, implying that the astrocytic responses resulted from seizure activity rather than neural injuries. Furthermore, astrocytes in malacic tissues disappeared during the severe limbic seizures. Therefore, it would be one of the cautionary notes on the expression of glial fibrillary acidic protein in astrocytes as a biochemical marker of brain injuries following acute exposure to organophosphates.

• 동의생리병리학회지
• /
• 제17권4호
• /
• pp.1031-1036
• /
• 2003

To certify the protective effect of herbal medicine against oxygen free radical-induced myocardiotoxicity, cytotoxicity was measured using TBARS assay and Beating rate in the presence of Tongryeong-san(TRS) extracts or single constituents of this prescription. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. In the present study, xanthine oxidase/hypoxanthine (XO/HX) resulted in a increase in lipid peroxidation and decreases in beating rate in cultured myocardial cells. In the effect of TRS extract, it showed the prevention from the XO/HX-induced cardiotoxicity by the increases of beating rate as well as the decrease of lipid peroxidation, In the protective effect of Faeces Trogopterori(FT), Pollen Typhae(PT), Caulis Akebiae(CA) and Radix Paeoniae Rubra(PRR), all the extracts were significantly effective in the protection of XO/HX-induced cardiotoxocity in cultured myocardial cells by the increase of beating rate as well as th decrease of lipid peroxidation. From these results, they show that XO/HX is cardiotoxic in cultured myocardial cells derived from neonatal rat, and it suggests that TRS, FT, PT, CA and PRR extracts are positively effective in the blocking in XO/HX-induced cardiotoxicity.

• Animal cells and systems
• /
• 제7권2호
• /
• pp.111-117
• /
• 2003

Ecological aspects of Cryptocercus kyebangensis life history were investigated via laboratory rearing and field observations. The number of antennal segments and head width were used to classify the first four instars. The results, which combine both the field collection and the laboratory rearing, indicate that eleven instars occur in C. kyebangensis. It supports the proposal on the number of instars of Park and Choe (2003c) based on field collections. A total of 388 nymps from 13 colonies were collected prior to winter to investigate overwintering stages. Of them,4％ (n = 17) were the second instars, 57％ (n = 220) were the third instars, and 39％ (n = 151) were the fourth instars, respectively. Thus, most of them overwinter in the third or fourth instars. The results indicate that young nymphs of C. kyebangensis have to reach at least 3rd or 4th instar to survive low temperature environment of winter. According to seasonal dynamics of populations, C. kyebangensis reaches adulthood in the summer of the fourth or fifth year (4-5 yr span) after their birth.

• IMMUNE NETWORK
• /
• 제23권6호
• /
• pp.45.1-45.22
• /
• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7195-7200
• /
• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• 동의생리병리학회지
• /
• 제21권4호
• /
• pp.1017-1024
• /
• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• Toxicological Research
• /
• 제27권3호
• /
• pp.173-180
• /
• 2011

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.