• IMMUNE NETWORK
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• 제21권4호
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• pp.26.1-26.28
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• 2021

Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4⁺ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.

• 한국동물학회지
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• 제35권3호
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• pp.295-307
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• 1992

In order to study the differentiation of the epithelial cells during the development of fetal rat lung tissue, histological changeB in organotypic culture and in vivo were examined. Light microscopy and scanning electron microscopy were used to analvre the histological change in rat lung from the 15th nary of gestation to the 111th nary after birth. In organotypic culture system, the pulmonary epithelial cell differentiation was studied by scanning electron microscopy. The results obtained from this study were as follows. 1. During deveiopment of lung, the glandular stage lasted from the Isth day to the lsth naut of gestation; the canalicular stage from the 17th nay to the 19th naut of gestation; the saccuiar stage from 20th nary to the birth. Alveolar stage was observed at the 3rd nary of postnatal rat lung. 2. In organotvpic culture of fetal rat lung cells organized alveolar-like structures resembling those of in uiuo state were observed on the gelatin matrix. In contrast with in vivo state, fetal lung cells formed group of type ll pneumocytes predominently along the contours of the matrix. These cells have large apical surface, short microvilli and secreted materials which may be sunactant. These results suggested that an orsanotypic culture retaining epithelial- -mesenchvmal relationships is appropriate culture model to study the pulmonary epithelial cell (especially type ll pneumocvte) differentation.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.171-176
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• 2012

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.

• Animal cells and systems
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• 제10권1호
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• pp.15-20
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• 2006

Allergic inflammation is thought to be a Th2 cell-dominant immune response during which tissue-resident fibroblasts produce chemokines which contribute to the recruitment of migratory leukocytes to sites of tissue injury. Thymus and activation-regulated chemokine (TARC; CCL17) is a potent member of the CC chemokine family and a selective chemoattractant for Th2 cells. In order to study the regulatory profiles of TARC production by $TNF-{\alpha}$, $IFN-{\gamma}$, and Il-4 in human normal skin fibroblast, CCD-986sk cell line was used. The expression of TARC protein was measured using ELISA, and mRNA level was detected by RT-PCR. The combination of $TNF-{\alpha}$ and IL-4 induced a time-and dose-dependent synergistic increase in the expression of TARC at both protein and mRNA levels in the cultured human skin fibroblasts. Exposure of the cells to single cytokine had no effect on TARC expression. The high concentration (100 ng/ml) and long incubation time (72 h) of $IFN-{\gamma}$ further enhanced the TARC production induced by $TNF-{\alpha}$/lL-4 in the skin fibroblast. This synergistic effect of Th1 and Th2 type cytokines on TARC production by skin fibroblasts may contribute to the inflammatory cell infiltration and tissue damage with allergic inflammation.

• Archives of Pharmacal Research
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• 제17권4호
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• pp.269-272
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• 1994

The effect of the root of Coptis japonica (COPT), both dichloromethane soluble $(CH_2Cl_2)$ and insoluble $(H_2O)$ fractions, on catecholamine contents and tyrosine hydorxylase (TH) activity in PC12 cells was investigated. $(CH_2Cl_2){\;}and{\;}H_2O$ fractions showed 21 and 53% inhibitions on dopamine content, respectively, at a ocncentraction of 40 .mu.g/ml in medium : the $(H_2O)$ fraction proveided a grateer inhibitory effect. The TH activity was reduced by the treatment of COPT ($(H_2O)$ fraction). These results suggest that COPT has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells.

• 약학회지
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• 제36권3호
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• pp.269-277
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• 1992

The effects of ginseng saponins on the distribution of nerve cells in cerebral cortex of carbon monoxide (CO)-intoxicated mice were studied in the young ($5{\sim}8$ weeks) and aged ($43{\sim}52$ weeks) mice. Mice were exposed to 5000 ppm of CO for 40 minutes (72% HbCO). After that, nerve cells in motor(area 4), somatosensory(area 3) and visual(area 17) area of cerebral cortex was observed. In young mice, the number of nerve cells in each area was significantly decreased on 1st, 7th and 14th day after CO intoxication. In aged mice, that was also decreased after CO intoxication. Especially the number of the nerve cells in motor and somatosensory area was significantly decreased on 1st and 7th day, while that in visual area was decreased only on 1st day. The number of nerve cells in young mice pretreated with ginseng saponins were significantly decreased less on 7th and 14th day than that of untreated mice. The number of nerve cells in each area of normal aged mice was larger than that of normal young mice. The results suggest that CO exposure causes local degeneration or disturbance of nerve cells and delayed neurologic sequelae, while ginseng saponins might play a role of protective action on the nerve cells which were damaged by CO.

• Journal of Animal Science and Technology
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• 제64권6호
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• pp.1184-1198
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• 2022

In this study, Rubus coreanus (R. coreanus) byproducts with high polyphenol content were fermented with R. coreanus-derived lactic acid bacteria (Lactobacillus plantarum GBL 16 and 17). Then the effect of R. coreanus-derived lactic acid bacteria fermented feed (RC-LAB fermented feed) with probiotics (Bacillus subtills, Aspergillus oryzae, Yeast) as a feed additive for pigs on the composition of intestinal microbes and the regulation of intestinal immune homeostasis was investigated. Seventy-two finishing Berkshire pigs were randomly allotted to four different treatment groups and 18 replicates. RC-LAB fermented feed with probiotics increased the genera Lactobacillus, Streptococcus, Mitsuokella, Prevotella, Bacteroides spp., Roseburia spp., and Faecalibacterium prausnitzii, which are beneficial bacteria of the digestive tract of pigs. Also, RC-LAB fermented feed with probiotics decreased the genera Clostridium, Terrisporobacter, Romboutsia, Kandleria, Megasphaera and Escherichia, which are harmful bacteria. In particular, the relative abundance of the genera Lactobacillus and Streptococcus increased by an average of 8.51% and 4.68% in the treatment groups and the classes Clostridia and genera Escherichia decreased by an average of 27.05% and 2.85% in the treatment groups. In mesenteric lymph nodes (MLN) and spleens, the mRNA expression of transcription factors and cytokines in Th1 and Treg cells increased and the mRNA expression of Th2 and Th17 transcription factors and cytokines decreased, indicating a regulatory effect on intestinal immune homeostasis. RC-LAB fermented feed regulates gut immune homeostasis by influencing the composition of beneficial and detrimental microorganisms in the gut and regulating the balance of Th1/Th2 and Th17/Treg cells.

• Childhood Kidney Diseases
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• 제22권1호
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• pp.17-21
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• 2018

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3137-3140
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• 2015

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

• IMMUNE NETWORK
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• 제20권5호
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• pp.40.1-40.15
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• 2020

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.