• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.391-396
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• 2014

Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

• 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.

• Animal cells and systems
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• 제12권3호
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• pp.127-136
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• 2008

Caspase-11 has been known as a dual regulator of cytokine maturation and apoptosis. Although the role of caspase-11 under pathological conditions has been well documented, its physiological role has not been studied much. In the present study, we investigated a possible physiological function of caspase-11 during immune response. In the absence of caspase-11, immunized spleen displayed increased cellularity and abnormal germinal center structure with disrupted microarchitecture. The rate of cell proliferation and apoptosis in the immunized spleen was not changed in the caspase-11-deficient mice. Furthermore, the caspase-11-deficient peritoneal macrophages showed normal phagocytotic activity. However, caspase-11-/-splenocytes and macrophages showed defective migrating capacity. The dysregulation of cell migration did not seem to be mediated by caspase-3, interleukin-$1{\alpha}$ or interleukin-$1{\beta}$ which acts downstream of caspase-11. These results suggest that a direct regulation of immune cell migration by caspase-11 is critical for the formation of germinal center microarchitecture during immune response. However, humoral immunity in the caspase-11-deficient mice was normal, suggesting the formation of germinal center structure is not essential for the affinity maturation of the antibodies.

• Journal of Plant Biotechnology
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• 제43권4호
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• pp.432-437
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• 2016

Interleukin-11 (IL-11) is a cytokine that plays a key regulatory role in the immune system. Recombinant human IL-11 (rhIL-11) exerts a preventative effect against apoptotic cell death and inhibits preadipocyte differentiation. IL-11 also is used to stimulate the bone marrow to produce platelets in order to prevent low platelets that may be caused by chemotherapy. Unfortunately, the high production cost of IL-11 associated. In this study, we investigated the feasibility of transgenic plants for the cost-effective production of rhIL-11. Production of rhIL-11 proteins in whole-plant expression system will be more economical when compared to the current E. coli based expression system. The human rhIL-11 gene was codon optimized to maximize plant host system expression. IL-11 expression vector under the control of a constitutive cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into tobacco by Agrobacterium-mediated transformation. The 5'-leader sequence (called ${\Omega}$) of tobacco mosaic virus (TMV) as a translational enhancer was added to construct. Transgenic tobacco plants expressing various levels of rhIL-11 protein were generated. Western blotting of the stably transformed lines demonstrated accumulation of the appropriately sized rhIL-11 protein in leaves. This research demonstrated the efficacy of using tobacco as an expression system for the production of rhIL-11.

• 한국임상수의학회지
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• 제17권2호
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• pp.311-315
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• 2000

Recombinant interleukin-2 (IL-2) has been demonstated as an antineoplastic agent in mice and human, and the route of administration is important to IL-2-induced therapeutic responses. Therefore, the current experiment was undertaken to clarify the effect of IL-2 administration route on antitumor response against subcutaneous Meth-A tumor in mice. At the beginning of each experiment, normal BALB/c mice were injected subcutaneously with $5{\times}10^6$ Meth-A tumor cells. Beginning on day 7, experimental groups were treated with a 5-day course of IL-2 (intraperitoneal or subcutaneous injection of 30, 000 IU every 12 hours for 5 days). The result of this experiment revealed that Meth-A tumor grew progressively in control mice. Intraperitoneal IL-2 treatment decreased significantly tumor growth and prolonged survival, compared with control mice. Subcutaneous IL-2 treatment decreased significantly tumor growth until day 11 and tumor cells, grew progressively thereafter, but mice in this group survived longer than control mice.

• The Korean Journal of Physiology and Pharmacology
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• 제11권6호
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• pp.259-262
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• 2007

Diffuse panbronchiolitis (DPB) is a pulmonary disease characterized by chronic inflammation of the bronchioles and chronic infiltration of inflammatory cells in the lungs. Macrolides are effective therapeutic agents for chronic respiratory tract diseases, such as DPB. However, the mechanisms by which macrolides modulate the immune responses in patients with DPB remain unclear. To understand clinical efficacy for the treatment of DPB by macrolides, the effects of erythromycin (EM) on the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) by human neutrophils were examined. Pre-treatment with EM significantly decreased the expression of IL-6 and IL-8 transcripts by lipopolysaccharide (LPS)-stimulated human neutrophils. EM also reversed the enhanced survival of human neutrophils by LPS. These data indicate that EM has achieved therapeutic effect for patients with DPB, in part, through decreasing the expression of pro-inflammatory cytokines and the survival of neutrophils.

• IMMUNE NETWORK
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• 제3권1호
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• pp.47-52
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• 2003

Background: The megakaryopoiesis and platelet production is regulated by several hematopoietc factors such as thrombopoietin (TPO), interleukin-11 (IL-11) and interleukin- 3 (IL-3). IL-11 is a potent stimulator of megakaryopoiesis in vivo, and acts primarily as a megakaryocyte maturation factor in vitro and it can act synergistically with IL-3 and TPO. We performed this study to investigate the effects of recombinant human IL-11 (rhIL-11) with other hematopoietic factors on megakaryocyte colony formation in vitro. Methods: CD34+ cells were separated from umbilical cord blood and megakaryocyte colonies using MegaCult Assay Kit were cultured with rhIL-11, recombinant human IL-3 (rhIL-3), and recombinant human TPO (rhTPO) for 7 and 14 days. The number and percentage of CD34+ and CD41a+ cells were determined by flowcytometry. Results: The number of CD41a+ cells were $0.54{\pm}0.05{\times}10^4$ (rhIL-11 100 ng/ml), $5.32{\pm}0.23{\times}10^4$ (rhIL-3 100 ng/ml), and $8.76{\pm}0.15{\times}10^4$ (rhTPO 50 ng/ml) of total expanded cells during the culture of the purified CD34+ cells in liquid phase for 7 days. The number of CD41a+ cells were increased to $7.47{\pm}0.69{\times}10^4$ (rhIL-3+ rhIL-11), $11.92{\pm}0.19{\times}10^4$ (rhTPO+rhIL-11) of total expanded cells, respectively, during the culture of the purified CD34+ cells in liquid phase for 7 days in the presence of rhIL-11 (100 ng/ml). When the purified CD34+ cells were cultured in semisolid mediaincluding various concentration of rhIL-11, the megakaryocyte colonies were not formed. When the purified CD34+ cells were cultured with rhIL-11 and rhTPO or with rhIL-11 and rhIL-3, the number of megakaryocyte colonies were increased compared with rhTPO or rhIL-3 alone. Conclusion: These results indicate that IL-11 exerts a potent proliferative activity to colony forming unit-megakaryocyte from human umbilical cord blood, and it acts with other hematopoietic factors synergistically.

• Journal of Microbiology and Biotechnology
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• 제15권6호
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• pp.1304-1309
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• 2005

The production of therapeutic proteins for human diseases in plants results in many economic benefits, including reduced risk of animal virus contamination, high yields, and reduced production and storage costs. Human cytokines, interleukin-11 (hlL-11) and granulocyte-macrophage colony-stimulating factor (hGM-CSF), cDNAs were introduced into rice or tobacco, using either the maize ubiquitin promoter or the 35S promoter. The primary hIL-11 transgenic rice plants exhibited stunted growth and a sterile phenotype, whereas the hIL-11 transgenic tobacco plants did not. This suggests that hIL-11 expression in rice disrupts the normal growth and development of the plant. The regeneration efficiency of rice calli transformed with hGM-CSF was found to be approximately a quarter of that seen with the hIL-11, suggesting that hGM-CSF expression is more deleterious to the regeneration of rice calli than is hIL-11. However, the surviving hGM-CSF transgenic rice plants exhibited a normal phenotype of growth. Therefore, it appears that only those transgenic rice lines that expressed the human cytokines in small quantities were able to survive the selection process.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.276-280
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• 2000

In order to identify the domains of the G$_{\alpha}$16 subunit G protein that are responsible for its activation by the Interleukin-8 receptor, a serious of chimeras between G$_{\alpha}$16 and G$_{\alpha}$11 were assessed for their abilities to be activated by these receptors. Co-expression of IL-8 receptor and chimeras in which the carboxyl-terminal regions of G$_{\alpha}$11 were replaced from 30 up to 156 amino acid residues with the corresponding regions of G$_{\alpha}$16 demonstrated that C-terminal 156 amino acid residues of the G$_{\alpha}$16 were not sufficient to confer IL-8 receptor interaction specificity. Testing of a reciprocal serious of chimeras composed of G$_{\alpha}$16 sequences at the amino terminus and G$_{\alpha}$11 sequences at the carboxyl terminals revealed that sequences extending from the amino tar- minus to amino acid 209 of G$_{\alpha}$16 were sufficient to 7ndow the chimera with 75-80% of interaction specificity for 7-8-induced activation. These results suggest th,.7t combined interactions of the C-terminal 30 amino acid residues and certain domains extending from the arts.ino terminus to amino acid 209 of Gal 6 protein may be involved in its couplings to IL-8 receptor.tain domains extending from the arts.ino terminus to amino acid 209 of Gal 6 protein may be involved in its couplings to IL-8 receptor.

• Tuberculosis and Respiratory Diseases
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• 제49권5호
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• pp.568-575
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• 2000

연구배경 : Cytokine은 주요한 염증 매개 물질로서 질환에 따라 다른 양상을 보일 수 있어, 흉수를 일으키는 다양한 원인 질환의 감별에 이용되어 왔다. 이 중에서 악성 흉수, 결핵성 흉수, 부폐렴 삼출액 및 농흉에서 INF-${\gamma}$, IL-2R, IL-6, IL-1를 동사에 측정하여 비교한 연구는 많지 않아 본 연구를 시행하게 되었다. 방법 : 흉수를 주소로 내원한 환자 중에서 흉수 천자로 삼출액이 확인된 환자들을 대상으로 흉수를 채취하여, ELISA kit를 이용하여 INF-${\gamma}$, IL-2R, IL-6, IL-10 농도를 측정하였다. 결과 : 악성 흉수, 결핵성 흉수, 부폐렴 삼출액 및 농흉에서 흉수 내의 cytokine의 순서대로, INF-${\gamma}$는 $16.7{\pm}50$, $295.5{\pm}585.5$, $10.0{\pm}0$ pg/ml, IL-2R은 $3247.4{\pm}1713.3$, $7423.5{\pm}3752.8$, $3790.2{\pm}3201.1$ pg/ml, IL-6는 $600{\pm}12.8$, $556.4{\pm}161.7$, $514.4{\pm}224.8$ pg/ml, IL-10은 $28.2{\pm}55.5$, $11.3{\pm}11.7$, $98.4{\pm}141.7$ pg/ml로 각각 측정되어, 결핵성 흉수가 다른 원인의 흉수에 비해 IL-2R 농도가 의 있게 높았으며, IFN-${\gamma}$ 농도도 높은 경향을 나타내었으며, 부폐렴 삼출액에서는 IL-10농도가 다른 원인의 흉수에 비해 의미있게 높았다. 결론 : 결론적으로 흉수 내의 IL-2R농도 측정은 결핵성 흉수와 다른 원인의 흉수를 감별하는데 어느 정도 도움이 될 것으로 사료되며, IL-10 측정은 부폐렴 삼출액과 다른 원인의 흉수를 감별하는데 어느 정도 도움을 줄 것으로 생각된다.