• Biomedical Science Letters
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• v.3 no.2
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• pp.139-150
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• 1997

In order to investigate the effect of aging and the $H_2O$$_2$ localization in association with histological, ultrastructural, and cytochemical studies in lung tissue after interleukin-1$\alpha$(IL-1) induced lung injury, an acute lung injury was induced by instillation of IL-1 into the trachea. Both of 4- and 20-months-old male rats, protein contents in IL-1 treated branchoalveolar lavage increased significantly compared to each control rats. Acute lung injury occured by oxidative stress because neutrophils accumulated in vascular lumen and formed the adhesion with endothelial cells. As these cause, tissue proteins were exuded and leukocytes migrated into the alveolar lumen. Neverthless in these lung injury $H_2O$$_2$ localization of IL-1 treated 20 months rats was not different compared to IL-1 treated 4 months rats. After all aging was not a factor to accelate IL-1 induced lung injury. Based on these results, it is suggested that neutrophil infilteration might be an important cause in acute lung injury, and aging is not a factor to change the acute lung injury by oxidative stress.

• BMB Reports
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• v.52 no.4
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• pp.283-288
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• 2019

$Foxp3^+$ regulatory $CD4^+$ T (Treg) cells play an essential role in preventing overt immune responses against self and innocuous foreign antigens. Selective expansion of endogenous Treg cells in response to the administration of interleukin (IL)-2/antibody complex, such as the IL-2/JES6-1 complex (IL-2C) in mice, is considered an attractive therapeutic approach to various immune disorders. Here, we investigated the therapeutic potential of IL-2C in allergic airway inflammation models. IL-2C treatment ameliorated Th17-mediated airway inflammation; however, unexpectedly, IL-2C treatment exacerbated Th2-mediated allergic airway inflammation by inducing the selective expansion of Th2 cells and type-2 innate lymphoid cells. We also found that IL-2 signaling is required for the expansion of Th2 cells in lymphoproliferative disease caused by Treg cell depletion. Our data suggest that IL-2C is selectively applicable to the treatment of allergic airway diseases depending on the characteristics of airway inflammation.

• Restorative Dentistry and Endodontics
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• v.30 no.3
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• pp.193-203
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• 2005

The induction of the IL-8 and MCP-1 by the stimulation of Substance P and TNF-${\alpha}$ (IL-8 agonist) and the specificity for SP using Spantide (SP antagonist) in the dental pulp tissues was measured quantitatively. In addition, the secretion of the IL-8 in the human dental pulp tissue 36 hrs after the stimulation of SP was observed after the stimulation of SP qualitatively. According to this study the results were as follows: 1. There was the significant IL-8 induction at 36 h after SP (10$^{-4}$M) stimulation of the pulp tissue comparing with the unstimulated dental pulp tissues (p < 0.05) . IL-8 irnmunostaining was weakly detected along the periphery of the pulp tissue after Mock stimulation and IL-8 immunostaining was detected around the fibroblast in the pulp tissue 36h After SP (10$^{-4}$M) stimulation, 2. The secretion of MCP-1 from the dental pulp tissues comparing with Mock stimulation was induced at 36 hrs after TNF-$\alpha$ (40 ng/ml) stimulation, but no induction with SP(10$^{-4}$M) TNF-${\alpha}$ (40 ng/ml) did not induce the IL-8 secretion from the pulp tissue, weak IL-8 imrnunostaining was detected along the periphery of the pulp tissue 3. Spantide (10$^{-5}$M) inhibited IL-8 induction from the pulp tissues 36 h after SP (10$^{-4}$M) stimulation These results suggest that SP significantly induces IL-8 recruiting neutrophils in localized human dental pulp tissue MCP-1 appears to be less involved in the early establishment of pulpal inflammation in response to irritation such as mechanical insult of dentin. SP may have positive relation with the inflammation of the human dental pulp tissues.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.299-310
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• 2005

The severe form of chronic periodontitis(CP) has been reported to be strongly associated with the presence of allele 2 of composite IL-1B(+3954) and IL-1A(+4845) genetic polymorphisms(genotype positive). However, other studies have reported conflicting findings. These might have resulted from differences in ethnic background and disease entities. The aim of this study was to determine the distribution of IL-1A(+4845), IL-1B(+3954), IL-1B(-511), and IL-1 RN(VNTR) genetic polymorphisms in children as a future Korean population. The study population consisted of 92 children from the Dept. of Pediatric Dentistry, Chonnam National University Hospital. Genomic DNA was obtained from buccal swab. The IL-1A(+4845), IL-1B(+3954), and IL-1B(-511) genes were genotyped by amplifying the polymorphic region using multiplex polymerase chain reaction(PCR), followed by restriction enzyme digestion and gel electrophoresis. IL-1 RN(VNTR) polymorphism were then evaluated by PCR amplification and fragment size analysis in agarose gel. The allele 2 frequency was 41.3%, 4.3%, 47.8%, and 9.9% for IL-1A(+4845), IL-1B(+3954), IL-1B(-511), and IL-1 RN respectively. The frequency of genotype with allele 2 carriage for IL-1A(+4845), IL-1B(+3954), IL-1B(-511), and IL-1 RN was 77.1%, 7.6%, 63.0%, and 15.2% respectively. The allele 2 frequency in IL-1B(+3954) was significantly higher in female than in male population(p<0.05). The negative association was shown between the presence of allele 2 in IL-1B(-511) and in IL-1B(+3954), and the carriage rate of IL-1B(+3954) allele 2 tended to lower in IL-1B(-511) allele 2(P=0.056). Only 7.3% of children carried the composite genotype of IL-1A(+4845) and IL-1B(+3954). These results suggest that the polymorphism of IL-1B(+3954) and the positive composite genotype was relatively rare in Korean population.

• Journal of Life Science
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• v.22 no.12
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• pp.1637-1643
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• 2012

This study investigated the effects of PG on IL-$1{\beta}$ expression and determined cellular factors involved in PG-mediated IL-$1{\beta}$ up-regulation in mononuclear cells in order to understand the molecular mechanisms underlying inflammatory responses associated with bacterial pathogen-associated molecular patterns in the diseased artery. Exposure of human monocytic leukemia THP-1 cells to PG resulted in enhanced secretion of IL-$1{\beta}$ and also profound induction of the IL-$1{\beta}$ gene transcript. These effects were abrogated by OxPAPC, an inhibitor of TLR-2/4. Pharmacological inhibitors such as U0126, SP6001250, Akti IV, rapamycin, and DPI also significantly attenuated PG-mediated IL-$1{\beta}$ up-regulation. However, polymyxin B did not influence the IL-$1{\beta}$ expression. This study indicates that PG contributes to vascular inflammation in atherosclerotic plaques by up-regulating expression of IL-$1{\beta}$ via TLR-2, Akt, mTOR, MAPKs, and ROS.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.100-109
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• 2015

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

• Journal of Microbiology and Biotechnology
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• v.11 no.2
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• pp.234-241
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• 2001

The C-terminal 393 bp region of the human interleukin-16 (IL-16) gene was cloned and expressed in E. coli along with mammalian cell lines. Recombinant IL-16 expressed from E. coli was 22 kDa on SDS-PAGE and showed 260% of chemoattractant activity at a concentration of $0.1\;{\mu}g/ml$. HeLa, COS, and Neuro-2a cells were transduced by recombinant retrovirus vector pLNC/IL-16/IRES/TK and the intracellular and secreted amounts of IL-16 produced by HeLa/IL-16/TK, COS/IL-16/TK, and Neuro-2a/IL-16/TK cells were determined by enzyme-linked immunosorbent assay (ELISA). HeLa/IL-16/TK $(1{\times}10^5)$ and COS/IL-16/TK $(1{\times}10^5)$ cells secreted 36.1 and 13.3 ng of IL-16 for 48 h, respectively. Forty-nine ng and 86.4 ng of IL-16 remained in the cell lysates of HeLa/IL-16/TK and COS/IL-16/TK. Intracellular and secreted amounts of IL-16 from Neuro-2a/IL-16/TK $(5{\times}10^5)$ cells during 24 h cultivation were 50 ng and 3.3 ng, respectively. Also, HeLa and COS cells wee stably transfected with mammalian expression vector pCRIII/IL-16. Both culture media and cell lysates prepared from HeLa/IL-16 cells and COS/IL-16 cells showed chemoattractant activity ranging from 190% to 460% as compared to the control experiment. Expression of the herpes simplex virus thymidine kinase (HSV0tk) gene in pLNC/IL-16/ IRES/TK bicistronic retroviral expression vector was verified by performing a genciclovir (GCV) sensitivity assay. Finally, IL-16 repressed Tat-transactivated human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) promoter activity.

• Korean Journal of Acupuncture
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• v.29 no.3
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• pp.406-420
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• 2012

Objectives : Scutellaria barbata has been widely used in oriental medicine used for treatment of acute and chronic inflammatory diseases. In this study, to investigate the protective effect of Scutellaria barbata on type I allergic response, we determined whether Scutellaria barbata inhibits early or late allergic responses. Methods : To assess the effect of Scutellaria barbata Pharmacopuncture Extract(SB) in RBL-2H3 cells, we investigated the levels of the markers of degranulation such as ${\beta}$-hexosaminidase and histamine, inflammatory mediator such as IL-4, TNF-${\alpha}$, PGE2 and cysLT, and mRNA expression of cytokines and enzymes. In addition, we determined the levels of intracellular ROS by DCFH-DA assay and the free radical scavenging activity by DPPH method. Results : We found that SB suppressed the release of ${\beta}$-hexosaminidase and histamine and the production of IL-4, TNF-${\alpha}$, PGE2 and cysLT in RBL-2H3 by the antigen stimulation. SB also significantly inhibited the enzyme mRNA expressions, such as HDC2, COX-1, COX-2, 5-LOX and iNOS2, along with reduced cytokine mRNA expressions, such as IL-$1{\beta}$, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF in RBL-2H3. In addition, SB suppressed the levels of intracellular ROS. Conclusions : Our results indicate that SB protects against type I allergic response and exert an anti-inflammatory effect through the inhibition of degranulation, inflammatory mediator release and mRNA expression of cytokines and enzymes.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1109-1114
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• 2021

Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.