• Clinical and Experimental Pediatrics
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• 제56권5호
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• pp.218-223
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• 2013

Purpose: Early diagnosis and treatment of acute pyelonephritis in children is of special importance in order to prevent serious complications. This study was conducted to determine the diagnostic value of serum interleukin (IL)-6 and IL-8 in children with acute pyelonephritis. Methods: Eighty-seven patients between 1 month to 12 years old with urinary tract infection (UTI) were divided into 2 groups based on the result of 99m-technetium dimercapto-succinic acid renal scan: acute pyelonephritis (n=37) and lower UTI (n=50) groups. White blood cell (WBC) count, neutrophil (Neutl) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) concentration, platelet count, and serum IL-6 and IL-8 concentrations of both groups were measured and compared. Results: There was a significant difference between two groups regarding WBC count, Neutl count, ESR, and CRP concentration (P<0.05). In addition, the difference between the two groups regarding serum IL-6 and IL-8 concentrations was not significant (IL-6, 60 and 35.4 pg/mL and IL-8, 404 and 617 pg/mL, respectively). The sensitivity and specificity of serum IL-6 and IL-8 for diagnosis of acute pyelonephritis were 73%, 42% and 78%, 32%, respectively. Sensitivity, specificity, negative and positive predictive values of serum IL-6 and IL-8 were less than those of acute phase serum reactants such as CRP. Conclusion: This study showed that there was no significant difference between acute pyelonephritis and lower UTI groups regarding serum IL-6 and IL-8 levels. Therefore, despite confirming results of previous studies, it seems that IL-6 and IL-8 are not suitable markers for differentiating between acute pyelonephritis and lower UTI.

• 대한치과교정학회지
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• 제43권6호
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• pp.294-301
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• 2013

Objective: To determine the interleukin (IL)-6 levels in gingival crevicular fluid (GCF) of patients with severe root resorption after orthodontic treatment and investigate the effects of different static compressive forces (CFs) on IL-6 production by human periodontal ligament (hPDL) cells and the influence of IL-6 on osteoclastic activation from human osteoclastic precursor (hOCP) cells in vitro. Methods: IL-6 levels in GCF samples collected from 20 patients (15 and 5 subjects without and with radiographic evidence of severe root resorption, respectively) who had undergone orthodontic treatment were measured by ELISA. The levels of IL-6 mRNA in hPDL cells and IL-6 protein in conditioned medium after the application of different uniform CFs (0, 1.0, 2.0, or 4.0 $g/cm^2$ for up to 72 h) were measured by real-time PCR and ELISA, respectively. Finally, the influence of IL-6 on mature osteoclasts was investigated by using hOCP cells on dentin slices in a pit-formation assay. Results: Clinically, the IL-6 levels were significantly higher in the resorption group than in the control group. In vitro, IL-6 mRNA expression significantly increased with increasing CF. IL-6 protein secretion also increased in a time- and magnitude-dependent manner. Resorbed areas on dentin slices were significantly greater in the recombinant human IL-6-treated group and group cultured in hPDL cell-conditioned medium with CF application (4.0 $g/cm^2$) than in the group cultured in hPDL cell-conditioned medium without CF application. Conclusions: IL-6 may play an important role in inducing or facilitating orthodontically induced inflammatory root resorption.

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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• pp.285-294
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• 2024

Myocardial infarction is one of the leading causes of mortality globally. Currently, the pleiotropic inflammatory cytokine interleukin-6 (IL-6) is considered to be intimately related to the severity of myocardial injury during myocardial infarction. Interventions targeting IL-6 are a promising therapeutic option for myocardial infarction, but the underlying molecular mechanisms are not well understood. Here, we report the novel role of IL-6 in regulating adverse cardiac remodeling mediated by fibroblasts in a mouse model of myocardial infarction. It was found that the elevated expression of IL-6 in myocardium and cardiac fibroblasts was observed after myocardial infarction. Further, fibroblast-specific knockdown of Il6 significantly attenuated cardiac fibrosis and adverse cardiac remodeling and preserved cardiac function induced by myocardial infarction. Mechanistically, the role of Il6 contributing to cardiac fibrosis depends on signal transduction and activation of transcription (STAT)3 signaling activation. Additionally, Stat3 binds to the Il11 promoter region and contributes to the increased expression of Il11, which exacerbates cardiac fibrosis. In conclusion, these results suggest a novel role for IL-6 derived from fibroblasts in mediating Stat3 activation and substantially augmented Il11 expression in promoting cardiac fibrosis, highlighting its potential as a therapeutic target for cardiac fibrosis.

• Tuberculosis and Respiratory Diseases
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• 제55권2호
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• pp.140-153
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• 2003

연구배경 : 결핵균 항원으로 세포 매개성 면역반응이 활성화되면 여러 종류의 cytokine이 분비되고 각기 다른 cytokine과 network system으로 작용하여 여러 병태생리적인 과정을 조절한다. 결핵 환자에서 염증반응, 조직파괴 및 질환의 중증도는 proinflammatory cytokine과 suppressive cytokine의 균형과 조합에 의하여 결정되며, 결핵 진행의 제한과 악화에 중요한 역할을 할 것으로 생각되고 있다. 따라서 결핵의 이환과정에서 cytokine의 분비 및 변화와 역할을 파악하는 것이 질환의 병태생리를 이해하는데 크게 도움이 될 수 있다. 대상 및 방법 : 활동성 폐결핵 83명, 기관지 결핵 10명의 치료전과 정상 대조군 20명에서 말초혈액을 채취하여 혈청을 분리하여 $-70^{\circ}C$에 보관하였고, sandwich ELISA 방법을 이용하여 혈청 IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$, TGF-${\beta}$를 측정하였다. 폐결핵 환자 83명을 ATS guideline에 따라 중증도를 분류하였고, 추적관찰 중 탈락자를 제외한 45명에서 초치료 2개월과 6개월 후 각각 혈청 sIL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$, TGF-${\beta}$를 재측정하였다. 결 과 : 1) IL-$1{\beta}$, TNF-${\alpha}$, IFN-${\gamma}$는 폐결핵 환자에서 대조군에 비하여 증가된 경향을 보였고(p>0.05), IL-6는 폐결핵군에서 통계적으로 유의하게 증가되었다(p<0.05). TGF-${\beta}$는 폐결핵과 기관지 결핵환자에서의 분비가 대조군에 비하여 감소된 경향을 보였으며(p>0.05), IL-2, IL-12(p40), IL-4, IL-10은 대조군과 폐결핵 환자에서 별다른 차이를 보이지 않았다. 2) 기관지 결핵 환자에서 IL-6, TNF-${\alpha}$는 대조군에 비해 증가되고 TGF-${\beta}$는 감소된 경향을 보였다(p>0.05). 폐결핵에 비해 IL-12(p40)의 분비는 증가된 경향을 보였다. 3) 결핵의 중증도가 심할수록 IFN-${\gamma}$와 IL-6가 유의하게 증가하였고(P<0.05), 특히 중증군에서 현저하였다. 4) 폐결핵 환자에서 치료전 측정한 IL-$1{\beta}$, IL-6, TNF-${\alpha}$ 간 및 IL-2, IL-4, IL-12 간에는 강한 양의 상관관계를 보였다(p<0.01). 5) 폐결핵 환자 45명에서 측정한 IL-6와 IFN-${\gamma}$는 치료후 2개월과 6개월에 각각 통계적으로 유의하게 감소되었다(p<0.05). 결 론 : 이상의 결과로 결핵의 병태생리에 있어서 여러 cytokine간의 균형과 조합의 변화가 숙주의 염증, 조직파괴 및 결핵의 중증도와 관련되어 있을 것으로 생각되지만 결핵의 형태나 면역반응 정도에 따른 다양성을 보여서 결과의 해석과 cytokine 측정의 임상적 이용에 대한 연구가 더욱 필요할 것으로 사료된다.

• 생명과학회지
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• 제18권12호
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• pp.1637-1643
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• 2008

HSP90에 노출된 혈관평활근세포에서 IL-6 transcript가 증가하고, IL-6 단백질의 분비가 증가하며, 또한 IL-6 유전자의 promote가 활성화되었다. HSP90에 의한 IL-6 유전자의 promoter 활성화는 dominant negative 형태의 TLR-4와 MyD88에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-3와 TRIF의 영향을 받지 않았다. 그리고 TLR-4의 이합체화(dimerization)를 저해하는 curcumin은 HSP90에 의한 IL-6의 분비 및 IL-6 유전자 promoter 활성화를 억제하였다. 그리고 IL-6 유전자의 promoter의 NF-${\kappa}B$- 또는 C/EBP-binding sequence에 변이는 HSP90에 의한 IL-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 IL-6 유전자 활성화에 TLR-4와 NF-${\kappa}B$B가 관여함을 의미한다.

• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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• pp.363-368
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• 2003

To gain insight on the role of pro-inflammatory cytokines in the pathogenesis and treatment of rheumatoid arthritis (RA), the phorbol 12-myristate 13-acetate (PMA)-induced IL-6 gene expression and the effect of caffeic acid phenethyl ester (CAPE) on the PMA-induced IL-6 gene expression were investigated in human fibroblast-like synoviocytes (FLSs). Synovial tissue samples were obtained from rheumatoid arthritis patients, and FLSs were isolated. The cells were stimulated with PMA (100 nM) for 6 hrs to induce IL-6 gene. The cells were pretreated with CAPE (20, 50, $100{\mu}M$) prior to PMA treatment. PMA increased IL-6 RNA expression, binding activities of transcription factors ($NF-{\kappa}B$, AP-1) to IL-6 promoter, and IL-6 promoter activity. However, CAPE inhibited PMA-induced IL-6 mRNA expression in dose-dependent manner, and also inhibited the increased binding activities of transcription factors to IL-6 promoter and IL-6 promoter activity. These results suggest that CAPE might regulate PKC-mediated IL-6 expression and inflammatory reactions in RA.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.426-430
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• 2014

Prostate cancer is the most frequently diagnosed cancer. Although prostate tumors respond to androgen ablation therapy at an early stage, they often acquire the potential of androgen-independent growth. Elevated transcriptional activity of androgen receptor (AR) and/or signal transducer and activator of transcription-3 (STAT3) contributes to the proliferation of prostate cancer cells. In the present study, we examined the effect of resveratrol, a phytoalexin present in grapes, on the reporter gene activity of AR and STAT3 in human prostate cancer (LNCaP-FGC) cells stimulated with interleukin-6 (IL-6) and/or dihydrotestosterone (DHT). Our study revealed that resveratrol suppressed the growth of LNCaP-FGC cells in a time- and concentration-dependent manner. Whereas the AR transcriptional activity was induced by treatment with either IL-6 or DHT, the STAT3 transcriptional activity was induced only by treatment with IL-6 but not with DHT. Resveratrol significantly attenuated IL-6-induced STAT3 transcriptional activity, and DHT- or IL-6-induced AR transcriptional activity. Treatment of cells with DHT plus IL-6 significantly increased the AR transcriptional activity as compared to DHT or IL-6 treatment alone and resveratrol markedly diminished DHT plus IL-6-induced AR transcriptional activity. Furthermore, the production of prostate-specific antigen (PSA) was decreased by resveratrol in the DHT-, IL-6- or DHT plus IL-6-treated LNCaP-FGC cells. Taken together, the inhibitory effects of resveratrol on IL-6- and/or DHT-induced AR transcriptional activity in LNCaP prostate cancer cells are partly mediated through the suppression of STAT3 reporter gene activity, suggesting that resveratrol may be a promising therapeutic choice for the treatment of prostate cancer.

• BMB Reports
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• 제52권3호
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• pp.214-219
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• 2019

The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

• 한국수정란이식학회지
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• 제31권4호
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• pp.323-333
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• 2016

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

• 대한미생물학회지
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• 제34권6호
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• pp.573-582
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• 1999

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. The purpose of this study was to investigate the effect of lipopolysaccharide (LPS), Staphylococcus enterotoxin B (SEB), and Mycoplasma lysates on regulation of IL-6 and IL-8 production by human nasal fibroblasts. Primary cultured cells were incubated with LPS ($1.0\;{\mu}g/ml$) from E.coli, SEB ($1.0\;{\mu}g/ml$) from S.aureus, or Mycoplasma lysates (M.pneumoniae, Mp; M. fermentans, Mf; M. hominis, Mh, each $1.0\;{\mu}g/ml$). The culture supernatants were collected at 2, 6, and 24 hr and assessed for IL-6 and IL-8 production by enzyme-linked immunosorbent assay. The production of IL-6 in the culture supernatant was downregulated by LPS, SEB, or Mycoplasma lysates. But IL-6 was upregulated by mixed exposure with Mp+LPS (2 hr), Mp+LPS+SEB (24 hr), Mf+LPS (24 hr), Mf+LPS+SEB (2 hr), Mh+LPS (24 hr), Mh+SEB (24 hr), or Mh+LPS+SEB (24 hr). The production of IL-8 in the culture supernatant was similar to that of IL-6 by same stimulants. But IL-8 was upregulated by mixed exposure with Mf+LPS+SEB (2 hr), Mh+LPS (24 hr), Mh+ SEB (24 hr), or Mh+LPS+SEB (24 hr). These studies show that costimulation of LPS or SEB with Mycoplasma whole cell lysates upregulates the production of IL-6 and IL-8.