• IMMUNE NETWORK
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• 제21권3호
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• pp.23.1-23.16
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• 2021

Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

• 생명과학회지
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• 제23권11호
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• pp.1409-1414
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• 2013

림프절은 체내로 침입한 병원체에 반응하여 성숙한 림프구들이 활성화 되는 곳이다. 림프구들은 스트로마의 구조적 뼈대를 따라 동계항원을 제시하고 있는 항원제시세포의 표면을 탐색한다. Fibroblastic reticular cells(FRC)는 림프절 T zone에서 3차원구조 네트워크를 형성하는데 관여하는 스트로마 세포로 유입되는 T 림프구들에 대한 안내길을 제공한다. 이런 상호 협력적인 환경에서 FRC와 T세포의 양방향적 관계는 림프절의 정상적 기능을 수행하는데 필수적이다. FRC는 물리적으로 림프절 조형물을 형성 할 뿐만 아니라 T세포 생물학적 기능조절에도 필수적이다. FRC는 T 림프구와 상호 반응하며 T세포에 발판을 제공하고 T세포 면역반응에 영향을 미치는 용해성 인자들을 방출한다. 최근에는 FRC는 말초에서 자기 관용 T세포 생성에도 관여하며 림프절에서 활성화된 T세포 분열을 조절하는데도 관여하고 있다. 따라서, FRC와 T세포 상호간 협력은 림프절에서 T세포기능을 조절하는데 중요한 결과를 야기한다. 더욱이, FRC는 염증 상황에서 항생펩타이드, 보체 등의 분비를 통한 선천성 면역에도 중요한 역할도 한다. 결론적으로 FRC와 T세포 상호간에 T세포 생물학적 효능을 증대를 위해 양방향성 접촉을 하며 이러한 상호 협력적 피드백은 면역반응 동안 조직기능 유지를 돕게 된다.

• IMMUNE NETWORK
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• 제11권3호
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• pp.169-174
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• 2011

Background: NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods: We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results: We investigated whether NOX2-deficiency affects T cell-mediated airway inflammation. Ovalbumin injection which activates T cell-mediated allergic response increased airway inflammation in wild-type mice, as evidenced by increased immune cell infiltration, allergic cytokine expression, and goblet cell hyperplasia in the lung. Interestingly, NOX2 knockout (KO) mice were more susceptible to allergen-induced lung inflammation compared to wild-type mice. Immune cells including neutrophils, lymphocytes, macrophages, and eosinophils were drastically infiltrated into the lung of NOX2 KO mice and mucus secretion was substantially increased in deficiency of NOX2. Furthermore, inflammatory allergic cytokines and eotaxin were significantly elevated in NOX2 KO mice, in accordance with enhanced generation of inflammatory cytokines interleukin-17 and interferon-${\gamma}$ by CD4+ T cells. Conclusion: These results indicate that NOX2 deficiency favorably produces inflammatory cytokines by T cells and thus increases the susceptibility to severe airway inflammation.

• Biomolecules & Therapeutics
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• 제13권3호
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• pp.174-180
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• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

• 한국식품영양학회지
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• 제19권2호
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• pp.201-206
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• 2006

Numerous investigators have studied various activities of natural products and have found that they have not only nutritional effects, but also beneficial properties to cure various diseases and to maintain good health. Job's Tear(Yul-Moo) is a grass crop that has long been used in traditional medicine and as a nourishing food. Although its mechanism of action remains unclear, Job's Tear has been reported to exhibit anti-inflammatory, stomachic, anti-allergic, and anti-spastic effects and has been used in China for the treatment of warts, rheumatism, and neuralgia. Previous results in our laboratory demonstrated that the ethanol extract and the water extract of Job's Tear exerted an immune regulatory function on mice cells in vitro. The present study was performed to investigate the ex vivo effect of Job's Tear on immune function. Seven to eight weeks old mice(Balb/c) were fed chow diet ad libitum and water extract of Job's Tear was administered orally every other day for four weeks at two different concentrations(50 and 500mg/kg B.W.). Splenocytes proliferation with mitogen stimulation with Con A and LPS was enhanced at 50 mg/kg B.W. of Job's Tear compared to those of the control group. The results of this ex vivo study showed that proliferation of splenocytes and macrophage activation were seen in the mice orally administrated 50 mg/kg B.W. of Job's Tear water extracts. In conclusion, this study suggests that Job's Tear extracts may enhance immune function by regulating splenocyte proliferation and the cytokine prodution capacity of activated macrophages in mice.

• Parasites, Hosts and Diseases
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• 제52권1호
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• pp.27-33
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• 2014

Mucosal immune responses against Pygidiopsis summa (Trematoda: Heterophyidae) infection were studied in ICR mice. Experimental groups consisted of group 1 (uninfected controls), group 2 (infection with 200 metacercariae), and group 3 (immunosuppression with Depo-Medrol and infection with 200 metacercariae). Worms were recovered in the small intestine at days 1, 3, 5, and 7 post-infection (PI). Intestinal intraepithelial lymphocytes (IEL), mast cells, and goblet cells were counted in intestinal tissue sections stained with Giemsa, astra-blue, and periodic acid-Schiff, respectively. Mucosal IgA levels were measured by ELISA. Expulsion of P. summa from the mouse intestine began to occur from days 3-5 PI which sustained until day 7 PI. The worm expulsion was positively correlated with proliferation of IEL, mast cells, goblet cells, and increase of IgA, although in the case of mast cells significant increase was seen only at day 7 PI. Immunosuppression suppressed all these immune effectors and inhibited worm reduction in the intestine until day 7 PI. The results suggested that various immune effectors which include IEL, goblet cells, mast cells, and IgA play roles in regulating the intestinal mucosal immunity of ICR mice against P. summa infection.

• 한국식품영양과학회지
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• 제44권11호
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• pp.1759-1762
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• 2015

시판 막걸리에서 분리한 균주(Lactobacillus paracasei ssp. paracasei M13-65-3)로 타락을 제조하였다. M13-65-3균주를 이용하여 제조한 타락 추출물에 의하여 T lymphocyte인 Jurkat 세포의 증식이 촉진되었고 피부세포의 멜라닌 생성이 억제되었다. 본 연구의 결과는 타락이 면역 증강 기능성과 피부색소 조절 기능성을 보유할 가능성을 제시하고 있다.

• 한국발생생물학회지:발생과생식
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• 제24권3호
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• pp.187-196
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• 2020

The caspase10 encodes an initiating caspase that plays an important role in the maintaining the cellular homeostasis by regulating the steps involved in the immune response and cell death. We investigated the expression of caspase10 during the different developmental stages and in olive flounder tissues. Caspase10 increased in the late stage of the formation of immune tissue, and high expression was observed in the gills, kidney, skin, and spleen. The current study analyzed the expressional changes of caspase10 in olive flounder infected with viral hemorrhagic septicemia virus (VHSV). One of the major causes of mass mortality, VHSV infection in olive flounder attributes to significant expression of caspase10 in the gills, spleen, skin, and kidneys. The results indicate a close association of caspase10 expression with the immune response to VHSV infection in olive flounder. The observations could form the basis data for exploration of other fish immune system.

• Natural Product Sciences
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• 제23권2호
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• pp.103-107
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• 2017

Angelica koreana is an important medicinal plant for some locals in East Asia including Korea. A few reports have shown the efficacy of its phytochemical constituents. We have isolated and purified one compound falcarindiol (FAL) from the methanolic extract of A. koreana roots. At concentrations from to $1{\mu}M$ to $25{\mu}M$, the FAL isolated from the roots of A. koreana exerted no significant cytotoxicity and down-regulated LPS-stimulated pro-inflammatory cytokine IL-8 in colon epithelial cells, while up-regulating anti-inflammatory cytokine IL-10. In addition, the FAL decreased the expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein by Western blot analysis. Colon epithelial cells play pivotal roles in regulating the colon immune system and thus FAL is expected to be candidate agent as therapeutic potential for the treatment of inflammatory bowel disease (IBD) by modulating LPS-induced inflammation in colon epithelial cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8119-8126
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• 2016

Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and ${\alpha}$-esterase activity. Extract treatment also attenuated any increases in serum levels of $TNF{\alpha}$, iNOS, IL-$1{\beta}$, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.