• 동의신경정신과학회지
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• 제12권2호
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• pp.157-171
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• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain

• 한국식품과학회지
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• 제36권6호
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• pp.986-990
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• 2004

대식세포는 IL-1, IL-6, $TNF-{\alpha},\;IFN-{\gamma}$의 중요한 근원이고, 전염성의 병원체와 종양 세포에 대해 저항하는 주요한 effector 세포이다. 이것은 cytokine signal에 의해 세포파괴가 되도록 활성화 된다. 이번 연구에서 우리는 산더덕의 물 추출물이 cytokine, nitric oxide와 같은 effector 분자를 유도하기 위해 대식세포를 활성화하는지를 알아보기 위하여 실험하였다. 산더덕 추출물에 의한 대식세포의 NO 생성은 농도 의존적이고, 시간 의존적이었다. iNOS는 시간이 지날수록 발현이 유도되었다. 산더덕 추출물에 의한 IL-1과 IL-6 mRNA 유도는 시간 의존적으로 증가 되었고, 처리 후 24시간에 최고점에 도달하였다. 이것은 활성화된 대식세포가 종양세포를 죽일 수 있음을 말한다. $TNF-{\alpha}\;mRNA$의 양은 시간이 지나도 일정하였고, $IFN-{\gamma}\;mRNA$의 양은 산더덕 추출물의 처리 1시간 후에 빠르게 강화되었다. 이러한 결과로부터 산더덕은 효과적인 면역조절자이고 대식세포의 항종양활성을 강화함을 알 수 있다.

• Tuberculosis and Respiratory Diseases
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• 제78권1호
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• pp.8-17
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• 2015

Background: AMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease. Methods: To investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in $AMPK{\alpha}1$-deficient ($AMPK{\alpha}1$-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells. Results: Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in $AMPK{\alpha}1$-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-${\beta}$-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an $AMPK{\alpha}1$-specific small interfering RNA. Conclusion: $AMPK{\alpha}1$-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.

• 대한피부과학회지
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• 제56권10호
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• pp.609-613
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• 2018

Background: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. Objective: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). Methods: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. Results: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. Conclusion: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2577-2582
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• 2013

Objectives: Interleukin (IL) -10 is a potent cytokine with a dual ability to immunosuppress or immunostimulate. We aimed to explore the association of IL10 promoter polymorphisms with risk of gastric cancer (GC) in a Han population in Southwestern China. Methods: We enrolled 308 pairs of GC and control subjects from four hospitals and a community between October 2010 and August 2011 in a 1:1 matched case-control design. Demographic information was collected using a designed questionnaire. IL10-592 A>C and IL10-1082 A>G polymorphisms were determined by Sequenom MassARRAY analysis. Results: Patients with GC reported statistically higher proportions of family history of cancer (29.9% versus 10.7%, P<0.01) and alcohol drinking (54.6% versus 43.2%, P<0.01) than did controls. Similar results were observed in comparison between non-cardia GC patients and controls (P<0.01 and P=0.03). Variant genotypes of IL10-592 A>C and IL10-1082 A>G were not associated with overall GC risk (adjusted OR, 0.94, 95% CI, 0.66-1.33; adjusted OR, 1.00, 95% CI, 0.62-1.60). Sub-analysis showed that the IL10-592 AC/CC variant genotype was associated with decreased non-cardia GC risk (adjusted OR, 0.58; 95% CI, 0.36-0.95). No association was found between any of the IL10 haplotypes established from two polymorphisms and risk of non-cardia GC. Conclusions: In conclusion, our data do not link the two SNPs of IL10-592 and IL10-1082 with overall GC risk. We demonstrate that IL10-592 polymorphism is associated with protective effect against non-cardia GC. Our findings may offer insight into risk associated with the development of GC in this region.

• 농업과학연구
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• 제45권3호
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• pp.437-446
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• 2018

Lactoferrin is an iron-binding glycoprotein which is present in colostrum, milk, and other body secretions. Lactoferrin activities are associated with inflammatory and immune responses. The aim of this study was to investigate the effect of lactoferrin hydrolysates (LH) on the production of immunomodulatory factors such as inflammatory related cytokines (tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, interleukin (IL)-6, and interleukin (IL)-13) in Raw264.7 cells, which originated from murine macrophages. The results show that the Raw264.7 cells cultured in 3 types (whole, and above and below 10 kDa) of lactoferrin hydrolysates (LH) did not show any cytotoxicity in the cells. $TNF-{\alpha}$ decreased dose-dependently to 1,500 - 2,000 ng/mL by treatment with the 3 types of LH at 1, 50, $100{\mu}g/mL$, whereas the positive control, lipopolysaccharide (LPS), and negative control produced 2,450 and 1,000 ng/mL of $TNF-{\alpha}$, respectively, in the Raw264.7 cells. The treatment with the 3 types of LH (whole and above and below 10 kDa) at $50{\mu}g/mL$ produced about 20 - 28 ng/mL of $IL-1{\beta}$ at 3, 6, and 9 h, respectively, while the negative control produced 7 ng/mL, and LPS as the positive control produced 48 - 60 ng/mL. $TNF-{\alpha}$ and IL-6 expression was decreased dose-dependently by the 3 types of LH. The mRNA levels of IL-13 were slightly increased dose-dependently by the whole and above 10 kDa LH, but decreased dose-dependently by the below 10 kDa LH in the Raw264.7 cells. The results show that LH had immunomodulating effects on cytokine production in anti- and pro-inflammatory reactions as well as anti-allergic reactions.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.265-271
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• 2014

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

• Journal of Periodontal and Implant Science
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• 제41권3호
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• pp.149-156
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• 2011

Purpose: Globular adiponectin (gAd) is a type of adipocytokine, which is mainly produced by adipose tissue. It has been reported that gAd acts as a pro- as well as an anti-inflammatory factor. Interleukin (IL)-6 and IL-8 are pro-inflammatory cytokines. To investigate the role of gAd on periodontal tissues, the expression of adiponectin receptor 1 (AdipoR1) and the effect of gAd on the expression of IL-6 and IL-8 were investigated in periodontal ligament (PDL) and gingival fibroblasts. Methods: PDL and gingival fibroblasts were cultured from human periodontal tissues. gAd derived from Escherichia coli and murine myeloma cells were used. The expression of AdipoR1 was estimated by reverse transcription-polymerase chain reaction and western blot The expression of cytokines was measured by enzyme-linked immunosorbent assay. Results: PDL and gingival fibroblasts expressed both mRNA and protein of AdipoR1. gAd derived from E. coli increased the production of IL-6 and IL-8, but polymyxin B, an inhibitor of lipopolysaccharide (LPS), inhibited IL-6 and IL-8 production induced by gAd in both types of cells. gAd derived from murine myeloma cells did not induce IL-6 and IL-8 production in those cells. gAd derived from E. coli contained higher levels of LPS than gAd derived from murine myeloma cells. LPS increased production of IL-6 and IL-8 in PDL and gingival fibroblasts, but pretreatment of cells with gAd derived from murine myeloma cells did not inhibit LPS-induced IL-6 and IL-8 expression. Conclusions: Our results suggest that PDL and gingival fibroblasts express AdipoR1 and that gAd does not act as a modulator of IL-6 and IL-8 expression in PDL and gingival fibroblasts.

• 대한임상검사과학회지
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• 제55권4호
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• pp.306-313
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• 2023

패혈증은 병원성 감염에 의해 여러 장기에 나타나는 전신성 염증 반응으로, 현재로서는 유망한 치료제가 없다. Signal transducer and activator of transcription 3 (STAT3)은 세포 신호전달 전사 인자로서 항염증 및 염증 반응과 관련된 다양한 세포의 생물학적 과정에서 중요한 역할을 한다. Niclosamide는 FDA에서 승인된 구충제로 STAT3 조절에 관여한다고 알려져 있다. C57BL/6 마우스에 복강 주사로 지질 다당체 (lipopolysaccharide, LPS)를 투여해 패혈증을 유발하였고, Niclosamide를 LPS 주사 2시간 후에 경구 투여하였다. 본 연구에서 Niclosamide가 LPS로 유발된 패혈증 모델의 생존률과 폐 손상을 완화시켰고, 혈청 내 interleukin (IL)-6, 종양괴사인자(tumor necrosis factor-α, TNF-α), IL-1β, AST, ALT, LDH 수치를 유의하게 감소시켰다. 또한 폐 조직 면역 블롯을 통해 PI3K, AKT, NF-κB, STAT3 신호 전달 경로가 Niclosamide에 의해 조절되는 것을 확인하였다. Niclosamide는 LPS를 자극한 RAW 264.7 세포주에서 IL-6, TNF-α, IL-1β와 같은 염증성 사이토카인의 발현을 감소시켰으며, 또한 STAT3의 인산화를 감소시켰다. 본 연구를 통해 Niclosamide에 의한 STAT3 조절이 염증 반응을 억제함으로써 패혈증 모델에 대한 새로운 치료 전략을 제시하였다.

• Parasites, Hosts and Diseases
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• 제31권3호
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• pp.249-258
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• 1993

원발성 아메바성 수막뇌염을 야기하는 Naegleria fowleri를 사망율에 따라 $1{\;}{\times}{\;}10^4$개 아메바 영양형 접종군과. $1{\;}{\times}{\;}10^5$개 아메바 영양형 접종군으로 나누어 비장세포를 비특이 mitogen인 Phytohemagglutinin(PHA)과 특이항원인 N. fowleri Iysates로 자극하여 T 세포의 interleukin-2 생성정도를 측정하고 T 림프구의 아형 및 아세포화정도를 측정한 결과 N.fowleri 아메바 영양형 $1{\;}{\times}{\;}10^5$개 접종군에서의 마우스 사망율은 72.2%였으며 $1{\;}{\times}{\;}10^4$개 접종군에서의 마우스 사망율은 14.3%였다. 또한 IL릭 생성정도를 접종후 7, 14, 24일째 측정한 결과. 접종 후 14일째에는 두 실험군 모두에서 대조군과 비교하여 IL닉의 생성이 유의하게 감소하였으며 접종 후 24일째에는 두 실험군 모두에서 접종 후 14일째 보다는 증가하였으나 대조군과 비교하여 유의하게 억제되었다 비장세포내 T 림프구 아형의 변동은 전체 비장 림프구에 대한 $Thy-1.2^{+}{\;}T.{\;}L3T4^{+}{\;}T,{\;}Ly^{2+}{\;}T$ 세포는 N.fowleri아메바 영양형 $1{\;}{\times}{\;}10^5$개 접종군에서 접종 후 7일째 대조군과 비교하여 유의하게 증가하였고 접종 후 14일째와 24일째에는 대조군과 비교하여 유의한 차이가 없었다. 아메바 영양형 $1{\;}{\times}{\;}10^4$개를 접종시킨 실험군은 경과 일수에 관계없이 대조군과 비교하여 유의한 차이가 없었다. 비장세포내 T 세포의 DNA의 분획을 관찰한 결과 두 실험군 모두에서 접종 후 7일째에 S phase 분획이 가장 높이 증가하였으며 접종 후 14일과 24일째에도 대조군에 비하여는 유의하게 증가하여 있었다. 이상의 결과를 종합하여 볼 때, N.fowleri를 사망율을 기준으로 접종량을 달리하여 아메바 영양형 $1{\;}{\times}{\;}10^4$개 접종군과 $1{\;}{\times}{\;}10^5$개 접종군으로 나누어 접종하였을 때, 접종 후 7일을 전후하여 IL-2를 매개로 활성화되는 세포매개성 면역이 N.fowleri감염의 방어기작으로 작용하는 것으로 생각되며 아메바 접종 후 14일째에는 치명적인 수막뇌염으로 진행되어 비장세포의 IL-2의 생성능력이 매우 억제된 것으로 생각된다. 또한 IL-2 생성능력과 T 세포의 아세포화의 증가 및 T세포 아령의 수의 변동과는 잘 일치되지 않는 것으로 나타났다.