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( Manju Acharya ),( Jihun Jo ),( Anju Maharjan ),( Ravi Gautam ),( Daeun Lee ),( Changyul Kim ),( Yong Heo ) 한국동물실험대체법학회 2020 동물실험대체법학회지 Vol.14 No.1
Although immune suppressive drugs have contributed for the cancer chemotherapy, organ transplant, but their therapeutic efficacy is limited. This study aims to evaluate the immunological modulations induced by four representative immunosuppressive on THP-1 cell line. 75% cell viabilities were determined and four test concentrations, 0.01X, 0.1X, 0.5X, and vehicle control were chosen. Culture supernatants were collected at 24 h after lipopolysaccharide (LPS1 ㎍/㎖) activation in the presence of test substances. 27 target cytokines were measured through luminex system and relative cytokine production levels (RCPLs,%) were calculated. Cytokines with the RCPL below 100% at all the three concentrations were 21 including IL-1beta, -1ra, -2, -4, -5, -6, -7, -9, -10, -12, -13, -15, -17, Eotaxin, FGF-basic, GM-CSF, IFNγ, IP-10, MCP-1α, PDGF-BB, and VEGF in dexamethasone-treated cells. Concerning on cyclophosphamide, the RCPLs on 11 cytokines were less than 100% at all the 3 concentrations. Treatment of cyclosporine demonstrated 10 cytokines with below 100% RCPL at all the 3 concentrations. The RCPLs below 100% were observed with 22 cytokines including IL-1β, -1ra, -2, -4, -5, -6, -7, -9, -12, -13, -15, -17, Eotaxin, GFG-basic, G-CSF, GM-CSF, IFNγ, MCP-1, MIP-1α, PDGF-BB, TNFα, and VEGF from THP-1 cells treated with tacrolimus at all the 3 concentrations. The present study indicates that tacrolimus and dexamethasone are stronger immunosuppressants than cyclophosphamide and cyclosporine on THP-1 cell line.
화학물질들의 면역독성 모니터링을 위한 THP-1 수지상세포주 활용
( Manju Acharya ),( Ravi Gautam ),( Anju Maharjan ),조지훈 ( Ji-hun Jo ),이다은 ( Daeun Lee ),박현지 ( Hyunji Park ),김유빈 ( Yubin Kim ),박성민 ( Sungmin Park ),허용 ( Yong Heo ) 대구가톨릭대학교 자연과학연구소 2020 자연과학연구논문집 Vol.18 No.1
Alternative test methods have been developed for various areas of toxicologic evaluation including skin sensitization or irritation, eye irritation, genotoxicity, or carcinogenicity. Whereas, alternative test method, especially based on in vitro approach, for screening immunotoxic substances was not actively challenged and therein, no test guideline has not been officialized internationally. THP-1 dendritic cell line was chosen for developing in vitro alternative test method for screening immunotoxic chemical or medicinal substances. Regarding major pathway for immune suppression or non-specific immune enhancement, antigen presenting cell is considered as most important target immune cells. Two test substances representing immune-enhancement(ribavirin) or immune-suppression (cyclophosphamide) were tested whether production of cytokines or chemokines is differentially modulated through supplementation of 0.01x, 0.1x, and 0.5x 75% cell viability(CV75) concentration of those compounds. Cell culture supernatants were collected at 24 h after the activation with 1 ㎍/㎖ lipopolysaccharide. Relative cytokine production levels (% versus each vehicle control, RCPL) were calculated. Production of all 27 cytokines evaluated was confirmed, which included IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7,IL-8, IL-9,IL-10, IL-12, IL-13, IL-15, IL-17, Eatoxin, FGF basic, G-CSF, GM-CSF, IFNγ, IP-10, MCP-1, PDGF-BB, MIP-1α, MIP-1β, RANTES, TNFα, VEGF. Treatment of ribavirin demonstrated all the RCPL values over 100% at 0.01x and 0.1x CV75 concentration. Treatment of cyclosphosphamide demonstrated the RCPL values below 100%except IL-12(0.01x), IL-13(0.1x), MCP-1(0.01x), TNFα (0.01x, 0.1x, and 0.5x), and VEGF(0.01x, 0.1x, and 0.5x). This findings suggest that THP-1 cell line is a valuable cell line to develop an in vitro alternative test method for screening immunotoxic chemical substances.
Jo JiHun,Acharya Manju,K C Pramod Bahadur,Maharjan Anju,Lee DaEun,Gautam Ravi,Kwon Jung-Taek,Kim KilSoo,Kim ChangYul,Heo Yong,Kim HyoungAh 한국독성학회 2023 Toxicological Research Vol.39 No.3
Microplastics (MPs) have been recently recognized as posing a risk to human health. The adverse health effects of MP exposure have been recently reported, especially via the oral exposure route. The present study investigated whether subacute (4 week) exposure to polyethylene (PE) or polytetrafluorethylene (PTFE) MPs via gastric intubation caused immunotoxicity. Two different sizes of PE MPs (6.2 or 27.2 μm) and PTFE MPs (6.0 or 30.5 μm) were administered to 6-week-old mice of both sexes at 0 (corn oil vehicle control), 500, 1000, or 2000 mg/kg/day (n = 4/group). No significant differences were observed between groups in the major thymic or splenic immune cell populations, including thymic CD4+, CD8+, CD4+/ CD8+ T lymphocytes, and splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-gamma (IFNγ) to interleukin-4 (IL-4) in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo (48 h) was dosedependently decreased in female mice that received small- and large-size PTFE MPs. The IFNγ/IL-4 ratio was also decreased in the female mice dosed with large-size PE MPs. The serum IgG2a/IgG1 ratio was dose-dependently increased in male and female animals dosed with small-size PE MPs, in female animals dosed with large-size PTFE MPs, and in male animals dosed with small-size PTFE MPs. The present study implies that immune functions could be affected in animals exposed to MPs via gastric intubation. These effects are dependent on MP size, MP dose, MP polymer type, and mouse sex. Further investigations with longer exposure periods could be necessary to more clearly define the immunotoxic effects of MPs.
Anju Maharjan,JiHun Jo,Manju Acharya,SuJeong Yang,Ravi Gautam,Sojung Sin,Hyocher Kim,ChangYul Kim,Yong Heo,HyoungAh Kim 계명대학교 자연과학연구소 2020 Quantitative Bio-Science Vol.39 No.2
The paradigm of immune homeostasis between type-1 helper T cells (Th1) and type-2 helper T cells (Th2) has been extensively examined with respect to infectious diseases, autoimmune diseases, or tumor progression. Such studies have mostly relied on the profiling of cytokines/chemokines using animal studies or cell culture-based in vitro tests. No quantitative analyses have yet been systematically performed to determine the relationship between the various immune parameters in in vivo investigations. Using peripheral blood from 55 chicken husbandry workers or grapevine orchard workers, we obtained data for various immunologic markers as follows: proportion of major immune cell subpopulations, concentrations of plasma immunoglobulin subclasses, and levels of cytokines produced from activated peripheral blood mononuclear cells. Correlational analyses were carried out to examine the association between these parameters. As the IFN-γ:IL-13 ratio was strongly associated with the production levels of IFN-γ, TNF-α, and to the IFN-γ:IL-4 ratio, the IFN-γ:IL-13 ratio could prove to be a valuable monitoring index to examine Th1 or Th2 predominance. IL-17 levels correlated well with those of IFN-γ or TNF-α. Plasma levels of IgG4, a typical IgG subclass expressed upon the occurrence of allergic diseases, strongly correlated with IgG1 levels, suggesting the implication of IgG1 in allergic hyperreactivity. The proportion of cytotoxic T cells correlated significantly with levels of IFN-γ, and the proportion of natural killer T cells correlated well with IL-13 levels. These two cell types are sources for the production of IFN-γ and IL-3 respectively; hence, results of this study might provide potential monitoring markers for cytotoxic T cells or natural killer T cell-mediated immunoreactivity. Overall, the present study provides several putative candidates for the surveillance or prognosis of the in vivo alteration of humoral or cell-mediated immunity.