• Title/Summary/Keyword: IL-3

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IL-4-deficient Mice Aggravate Hypersensitivity Pneumonitis

  • Hwang, Su-Jin;Chung, Doo-Hyun
    • IMMUNE NETWORK
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    • v.8 no.3
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    • pp.90-97
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    • 2008
  • Background: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. Methods: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. Results: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-${\gamma}$, TGF-${\beta}$ and TNF-${\alpha}$ in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1${\alpha}$, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-${\gamma}$-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. Conclusion: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.

Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells

  • Hyo-Min Park;Jae-Young Park;Na-Yeon Kim;Hyemoon Kim;Hong-Gyum Kim;Dong-Ju Son;Jin Tae Hong;Do-Young Yoon
    • IMMUNE NETWORK
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    • v.24 no.3
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    • pp.27.1-27.14
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    • 2024
  • The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1β, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFβ, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

The Relationship Between the NF-${\kappa}B$ Activity and Anti-inflammatory Action of Surfactant in the Acute Lung Injury of Rats (백서의 급성폐손상에서 surfactant의 항염증작용과 호중구의 NK-${\kappa}B$ 활성과의 관계)

  • An, Chang-Hyeok;Cha, Young-Joo;Lee, Kyoung-Hee;Yoo, Chul-Gyu;Lee, Byoung-Jun;Jeong, Do-Young;Lee, Sang-Hoon;Shin, Jong-Wook;Kim, Jae-Yeol;Park, In-Won;Choi, Byoung-Whui
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.5
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    • pp.519-529
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    • 2002
  • Background : The therapeutic effects of surfactants on acute lung injury derive not only from their recruiting action on collapsed alveoli but also from their anti-inflammatory action in the alveolar sapce. This study evaluated the anti-inflammatory action of a surfactant in an acute lung injury model of rats by neutrophils were recollected from the BAL fluid and the NF-${\kappa}B$ activity of the neutrophilic nuclear protein was evaluated. Methods : Male Sprague-Dawley rats weighing approximately 300 gram were divided into 3 groups, which consisted of 6 rats respectively. In the control group, normal saline(3ml/kg) was instilled into the trachea twice with 30 minute interval. In two other groups, acute lung injury was induced by the intra-tracheal instillation of LPS(5mg/kg). Thirty minutes later, either a surfactant(ST group; 30mg/kg) or normal saline(NT group: 3ml/kg) was instilled via the trachea. Twenty-four hours after the LPS instillation, the BAL fluid was retrieved to measure the WBC count and cytokine(IL-$1{\beta}$ and IL-6) levels. The neutrophils were isolated from the BAL fluid and the nuclear protein was extracted to evaluate the NF-${\kappa}B$ activity using a eletrophoretic mobility shift assay(EMSA). Results : The WBC count of the BAL fluid of the ST group($3,221{\pm}1,914{\times}10^3/{\mu}l$) was higher than that of the control group($356{\pm}275{\times}10^3/{\mu}l$)(p<0.05) and lower than that of the NT group($5,561{\pm}1,757{\times}10^3/{\mu}l$)(p<0.05)). The BAL fluid level of IL-$1{\beta}$ from the NT group($2,064{\pm}1,082pg/ml$) was higher than those of the ST group($360{\pm}234pg/ml$)(p<0.05) and the control group(0pg/ml)p<0.05) and control group($49{\pm}62pg/ml$)(p<0.05). The NF-${\kappa}B$ activity of the neutrophilic nuclear protein in the ST group and NT group was similar. Conclusion : The surfactant, attenuates the alveolar inflammation in the acute lung injury of rats model. However, its anti-inflammatory action does no't appear to be mediated by the inhibition of NF-${\kappa}B$ activity.

NLRP3 Inflammasome in Neuroinflammatory Disorders (NLRP3 인플라마좀 작용 기전 및 신경 질환에서의 역할)

  • Kim, Ji-Hee;Kim, YoungHee
    • Journal of Life Science
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    • v.31 no.2
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    • pp.237-247
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    • 2021
  • Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.

The Effects of Soyumjungjang-tang on DSS-Induced Ulcerative Colitis in Mouse (소염정장탕(消炎整腸湯)이 DSS로 유발(誘發)된 생쥐의 궤양성 대장염에 미치는 영향(影響))

  • Song, Young-Guen;Ryu, Bong-Ha;Yoon, Seong-Woo
    • The Journal of Internal Korean Medicine
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    • v.29 no.2
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    • pp.385-400
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    • 2008
  • Objectives : This study was carried out to investigate the effects of Soyumjungjang-tang(SJT) on the experimental ulcerative colitis induced by dextran sulfate sodium(DSS) in mice. Methods : Ulcerative colitis was induced through supplying 4% DSS solution as the drinking water for 7 days in 6-week-old male ICR mice. The colitic mice were divided into three groups: the sample groups were orally administered SJT in doses of 25mg/kg(S25 group) or 100mg/kg(S100 group) once a day for 10 days, from 3 days before starting drinking the DSS solution, and the control(C) group was administered normal saline instead of SJT. The DSS solution or SJT was not administered to the normal(N) group. The length of colon, histologic finding, the activities of myeloperoxidase(MPO) and alkaline phosphatase(AP), and the expressions of $IL-1{\beta}$, IL-6, COX-2, $NF-{\kappa}B$, and $I{\kappa}B$ in colonic mucosa was checked using immunoblot, ELISA, etc. The activities of chondroitinase, tryptophanase, ${\beta}-glucuronidase$ and ${\beta}-glucosidase$ in stool were also measured. Results : The length of colon shortened, histologic finding deteriorated, the activities of MPO, AP, chondroitinase, tryptophanase, ${\beta}-glucuronidase$ and ${\beta}-glucosidase$, and the expressions of $IL-1{\beta}$, IL-6, COX-2, $NF-{\kappa}B$ increased, and the expression of $I{\kappa}B$ decreased in the C group. All measures, except $NF-{\kappa}B$, were restored in S25 group, but some measures deteriorated more in the S100 group than in the C group. Conclusions : According to the above results, it is supposed that SJT has a potential therapeutic effect on ulcerative colitis.

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Studying of the Effects of Cyperus rotundus L. extract on Th1/Th2 Cell-derived Cytokines (향부자(香附子)가 천식 관련 Th1/Th2 세포 관련 cytokine 분비에 미치는 영향)

  • Yom, David Jong-Hoon;Rhee, Hyung-Koo;Jung, Sung-Ki;Jung, Hee-Jae
    • The Journal of Internal Korean Medicine
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    • v.30 no.3
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    • pp.451-464
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    • 2009
  • Background and Objective : Cyperus rotundus L. (CR) is a commonly used herbal medicine in Asian countries such as Korea, China and Japan. The present study was designated to evaluate the direct effects of CR on helper T cell activities and on Th1/Th2 lineage development in vitro. Materials and Methods : Spleen cells from 8 week BALB/c mice were cultured in CR extracts containing medium without activation for 24 hours and with activation for 48 hours. CD4+ T cells were isolated and analyzed for mRNA expression levels of INF-$\gamma$, IL-4, T-bet and GATA-3 by RT-PCR and secretion cytokines levels of INF-$\gamma$, IL-4, IL-5 and IL-10 by ELISA. Results : The results demonstrated that CR had no mitogenic effects on unstimulated CD4+ T cells, but augmented CD4+ T-cell proliferation upon activation with anti-CD3/anti-CD28 antibodies in a dose-dependent manner. CR treatment significantly increased CD4+ T cell population and the IFN-$\gamma$ expression was significantly enhanced, while IL-4 expression was significantly decreased. In addition, in vitro Th1/Th2 polarization experiments revealed that CR enhanced IFN-$\gamma$ secretion in Th1 cells, but reduced the IL-4 in Th2 cells in a dose-dependent manner. Conclusion : These results suggest that CR treatment could be a desirable alternative therapy for the prevention or correction of Th2 dominant pathological disorders, such as allergy and asthma.

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Effect of Cinnamon Extract on the Inflammatory Response in the LPS-shock Rat

  • Lee, Eun
    • Korean Journal of Plant Resources
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    • v.28 no.3
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    • pp.333-340
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    • 2015
  • This study measured the plasma and liver concentrations of cytokines, the distribution of blood lymphocyte subpopulations (CD4 and CD8), plasma levels of nitrite (NO3) and nitrate (NO2), intercellular adhesion molecule 1 (ICAM-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), prostaglandin E2 (PGE2), and peritoneal lavage fluid (PLF) levels of monocyte chemotactic protein 1 (MCP-1) and CINC-1 in order to examine the anti-inflammatory activity of the cinnamon extract in lipopolysaccharide (LPS)-exposed rats. The plasma concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) were lower in the cinnamon extract groups than in the control group at both 2 and 5 h after LPS injection. Furthermore, the liver concentrations of IL-1β, IL-6, and TNF-α were lower in the cinnamon extract groups than in the control group at 5 h after LPS injection. Plasma IL-10 concentrations were higher in the cinnamon extract groups than in the control group at both 2 and 5 h after LPS injection, and liver concentrations of IL-10 did not differ significantly among all treatment groups at 5 h after LPS injection. The distribution of CD4 tended to increase, and that of CD8 tended to decrease in the cinnamon extract groups. The CD4/CD8 ratio was increased in the cinnamon extract groups. The plasma concentrations of NO3/NO2, ICAM-1, CINC-1, and PGE2 and the PLF concentrations of MCP-1 and CINC-1 exhibited a tendency to decrease in the cinnamon extract groups. These results indicate that cinnamon extract can exert functional anti-inflammatory effects.

The Experimental Study on the Anti-Allergic Rhinitis Effects of the Sinichengpae-um (신이청매음(辛夷淸肺飮)이 알레르기 비염(鼻炎)에 미처는 효과(效果)에 대한 실험적(實驗的) 연구(硏究))

  • Kang, Sang-Hun;Sim, Sung-Yong;Byun, Hak-Sung;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.18 no.3
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    • pp.18-25
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    • 2005
  • Objectives: It has a growing interest in the prevention and medical treatment of allergic rhinitis. According to many studies, it's known that Sinicheongpye-um has the inhibitory effect on the allergic rhinitis. We have studied effect of the mice on OVA-induced Production of IL-4, IL-5, $Interferone-{\gamma}$ by Murine Splenocytes and effect of OVA-induced Total IgE. Methods: Mixing Ovalbumin(OVA) $10{\mu}g$ into PBS(phoshate buffered saline) and $Al(OH)_3$, gel solution and changing into $1\;m{\ell}$, we made it into OVA solution. That was administered to normal group. After the last administration into abdominal cavity, we caused allergic rhinitis in nasal cavity of mouse of control group and sample group administering 0.1% solution dropwise 3 times a day for 7 days. Keeping separated serum at -20 degree and after refloating spleen cells, cultivating the cells and centrifuging the upper liquid and keeping it at -20 degree, we measured the amount of IL-4. IL-5, $Interferone-{\gamma}$ and OVA-induced Total IgE by ELISA. Results: 1. In Total IgE, Sinichengpae-um treated group was proved significant inhibitory effect.(p<0.05) 2. In IL-4 study, Sinichengpae-um treated group was proved significant inhibitory effect.(p<0.005) 3. In IL-4 study, Sinichengpae-um treated group was proved significant inhibitory effect.(p<0.001) 4. In $Interferone-{\gamma}$ study, Sinichengpae-um treated group showed a increasing tendency. Conclusion: Based on the above result, it is considered that Sinichengpae-um has the inhibitory effect on the allergic rhinitis of mice and suggested thai it could be used in relieving patients of the symptoms which are caused by allergic rhinitis.

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