• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.393-398
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• 2012

Mast cells are involved in allergic responses, protection against pathogens and autoimmune diseases. Dexamethasone (Dex) and other glucocorticoids suppress $Fc{\varepsilon}RI$-mediated release of inflammatory mediators from mast cells. The inhibition mechanisms were mainly investigated on the downstream signaling of Fc receptor activations. Here, we addressed the effects of Dex on Fc receptor expressions in rat mast cell line RBL-2H3. We measured mRNA levels of Fc receptors by real-time PCR. As expected, Dex decreased the mRNA levels of activating Fc receptor for IgE ($Fc{\varepsilon}R$) I and increased the mRNA levels of the inhibitory Fc receptor for IgG $Fc{\gamma}RIIb$. Interestingly, Dex stimulated transcriptions of other activating receptors such as Fc receptors for IgG ($Fc{\gamma}R$) I and $Fc{\gamma}RIII$. To investigate the mechanisms underlying transcriptional regulation, we employed a transcription inhibitor actinomycin D and a translation inhibitor cycloheximide. The inhibition of protein synthesis without Dex treatment enhanced $Fc{\gamma}RI$ and $Fc{\gamma}RIII$ mRNA levels potently, while $Fc{\varepsilon}RI$ and $Fc{\gamma}RIIb$ were minimally affected. Next, we examined expressions of the Fc receptors on cell surfaces by the flow cytometric method. Only $Fc{\gamma}RIIb$ protein expression was significantly enhanced by Dex treatment, while $Fc{\gamma}RI$, $Fc{\gamma}RIII$ and $Fc{\varepsilon}RI$ expression levels were marginally changed. Our data showed, for the first time, that Dex regulates Fc receptor expressions resulting in augmentation of the inhibitory receptor $Fc{\gamma}RIIb$.

• Journal of Chitin and Chitosan
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• v.23 no.4
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• pp.277-284
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• 2018

In this study, we investigated the anti-allergic effect of the ethyl acetate fraction of Ecklonia cava (EC-EtoAc) on the immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation of bone marrow-derived cultured mast cells (BMCMCs). We revealed that the $62.5{\mu}g/ml$ of EC-fractions ($EC-CHCl_3$, EC-Hexane and EC-EtoAc) inhibited IgE/BSA-activated ${\beta}$-hexosaminidase release from BMCMCs without cytotoxicity. Especially, EC-EtoAc showed the higher ${\beta}$-hexosaminidase release than the others. Also, EC-EtoAc reduced the expression levels of cytokines such as interleukin (IL)-$1{\beta}$, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$ and a chemokine, thymus- and activation-regulated chemokine (TARC), compared to the only IgE/BSA-treated BMCMCs. Furthermore, EC-EtoAc significantly prevented the binding of IgE to Fc epsilon receptor $(Fc{\varepsilon}R)I$ and reduced the $Fc{\varepsilon}RI$ expression on the sensitized BMCMCs. Taken together, these results suggest that E. cava may be the natural agent with beneficial potentials for the treatment of type I allergic diseases induced by mast cell activation.

• Journal of Sensor Science and Technology
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• v.20 no.6
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• pp.434-438
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• 2011

A portable surface plasmon resonance(SPR) based immunosensor using thiolated protein G and protein G was developed for the detection of immunoglobulin G(IgG). The protein G has specific affinity with Fc fragment of IgG and was thiolated by 2-Iminothiolane for introduction of thiol groups. Anti-IgG, bovine serum albumin(BSA), and IgG have been sequently injected after surface modification of gold sensor chip with protein G and thiolated protein G. The output signal was increased with the injection of each protein and the actual signal was measured by subtracting signal of reference channel from signal of sample injected channel. The experimental results showed the higher detection capability of IgG using thiolated protein G compared with protein G. From these results, we can conclude that the current surface modification technique and the portable SPR sensor system can be applied to various immunosensors for diagnosis.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1089-1095
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• 2012

Neonatal Fc receptor (FcRn) gene encodes a receptor that binds the Fc region of monomeric immunoglobulin G (IgG) and is responsible for IgG transport and stabilization. In this report, the 8,900 bp porcine FcRn genomic DNA structure was identified and putative FcRn protein included 356 amino acids. Alignment and phylogenetic analysis of the porcine FcRn amino acid sequences with their homologies of other species showed high identity. Tissues expression of FcRn mRNA was detected by real time quantitative polymerase chain reaction (Q-PCR), the results revealed FcRn expressed widely in ten analyzed tissues. One single nucleotide polymorphism (SNP) (HQ026019:g.8526 C>T) in exon6 region of porcine FcRn gene was demonstrated by DNA sequencing analysis. A further analysis of SNP genotypes associated with serum Classical Swine Fever Virus antibody (anti-CSFV) concentration was performed in three pig populations including Large White, Landrace and Songliao Black pig (a Chinese indigenous breed). Our results of statistical analysis showed that the SNP had a highly significant association with the level of anti-CSFV antibody (At d 20; At d 35) in serum (p = 0.008; p = 0.0001). Investigation of expression and polymorphisms of the porcine FcRn gene will help us in further understanding the molecular basis of the antibody regulation pathway in the porcine immune response. All these results indicate that FcRn gene might be regarded as a molecular marker for genetic selection of anti-CSFV antibody level in pig disease resistance breeding programmes.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.65-70
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• 2015

It is well known that proteins present in the primary urine are reabsorbed in the renal proximal tubules, and that this reabsorption is mediated via the megalin-cubilin complex and the neonatal $Fc{\gamma}$ receptor. However, the reabsorption is also thought to be influenced by an electrostatic interaction between protein molecules and the microvilli of the renal proximal tubules. By analyzing the charge diversity of urinary IgG, we showed that this reabsorption process occurs in a cationic charge-preferential manner. The charge-selective molecular sieving function of the glomerular capillary walls has long been a target of research since Brenner et al. demonstrated the existence of this function by a differential clearance study by using the anionic dextran sulfate polymer. However, conclusive evidence was not obtained when the study was performed using differential clearance of serum proteins. We noted that immunoglobulin (Ig) A and IgG have similar molecular sizes but distinct molecular isoelectric points. Therefore, we studied the differential clearance of these serum proteins (clearance IgA/clearance IgG) in podocyte diseases and glomerulonephritis. In addition, we studied this differential clearance in patients with Dent disease rather than in normal subjects because the glomerular sieving function is considered to be normal in subjects with Dent disease. Our results clearly showed that the charge-selective barrier is operational in Dent disease, impaired in podocyte disease, and lacking in glomerulonephritis.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.546-552
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• 2022

Epidermal cell adhesion molecule (EpCAM) is a tumor-associated antigen (TAA), which has been considered as a cancer vaccine candidate. The EpCAM protein fused to the fragment crystallizable region of immunoglobulin G (IgG) tagged with KDEL endoplasmic reticulum (ER) retention signal (EpCAM-FcK) has been successfully expressed in transgenic tobacco (Nicotiana tabacum cv. Xanthi) and purified from the plant leaf. In this study, we investigated the ability of the plant-derived EpCAM-FcK (EpCAM-FcK^P) to elicit an immune response in vivo. The animal group injected with the EpCAM-FcK^P showed a higher differentiated germinal center (GC) B cell population (~9%) compared with the animal group injected with the recombinant rhEpCAM-Fc chimera (EpCAM-Fc^M). The animal group injected with EpCAM-FcK^P (~42%) had more differentiated T follicular helper cells (Tfh) than the animal group injected with EpCAM-Fc^M (~7%). This study demonstrated that the plant-derived EpCAM-FcK fusion antigenic protein induced a humoral immune response in mice.

• BMB Reports
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• v.42 no.4
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• pp.212-216
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• 2009

The short in vivo half-life of GLP-1 prevents it from being used clinically. This short half-life occurs because GLP-1 is rapidly degraded by dipeptidyl peptidases such as DPP-IV. To overcome this obstacle, a GLP-1/Fc was constructed and evaluated to determine if it was degraded by DPP-IV and in serum. When the degradation of GLP-1/Fc by human DPP-IV and rabbit serum was compared with that of GLP-1 it was found to be reduced by approximately 5- and 4-fold, respectively. Furthermore, GLP-1/Fc showed a potent activity for human GLP-1 receptor activation ($EC_{50}$ approximately 6 nM). Taken together, these results indicate that GLP-1/Fc may have an extended half-life in vivo that occurs as a result of inhibition of degradation by human DPP-IV. Due to the extended half life, GLP-1/Fc may be useful for clinical treatments.

• Horticultural Science & Technology
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• v.32 no.3
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• pp.375-381
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• 2014

Transgenic potato was generated to express recombinant 5 repeated ${\beta}$-amyloid ($A{\beta}$) peptides, potential antigens to be applied as a preventive accine for Alzheimer's disease using Agrobacterium mediated transformation. The $A{\beta}$ peptides were fused to the human IgG Fc fragment enhancing protein and KDEL, which is the endoplasmic reticulum (ER) retention signal ($5A{\beta}$-FcK). The $5A{\beta}$-FcK, was expressed under the control of the duplicated 35S promoter. PCR analysis confirmed the presence of the transgene in several transgenic potato lines. Southern blot analysis showed only a single gene copy number in transgenic line 22, whereas multiple gene copy numbers were shown for transgenic lines 31 and 44. Northern blot analysis showed that line 22 had stronger mRNA levels when compared to lines 31 and 44. Immunoblot analysis confirmed that the $5A{\beta}$-FcK protein was expressed in the transgenic potato plant. These results indicate that $5A{\beta}$ fused to Fc can be expressed in potato plants.

• Journal of Periodontal and Implant Science
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• v.36 no.1
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• pp.113-123
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• 2006

연구배경 IgG에 대한 $Fc{\gamma}$ 수용기는 치주병인균에 대한 숙주 반응에 있어서 중요한 역할을 하는데, 이 중 $Fc{\gamma}RIIIa$는 NK 세포, 대식세포, 단핵구, ${\gamma}{\delta}T$세포에서 발현되며, EC2 도메인에서 158 아미노산 부위의 valine (V)-phenylalanine (F)의 유전자다형성을 보인다. $Fc{\gamma}RIIIb$는 특이적으로 중성구에 발현되는데, extracellular (ECl) Ig-like 도메인 내 4개의 아미노산 치환(substitutions)에 의한 NA1-NA2 유전자다형성을 보인다. 이 연구의 목적은 한국인에서 급진성 치주염 환자와 $Fc{\gamma}III$ 수용기의 유전자다형성과의 관련성을 알아보는 것이다. 연구방법 및 재료 치주적으로 건강한 90명 (대조군, 남자 64명, 여자 26명)과 서울대학교 치과병원 지주과에 내원하여 급진성 치주염으로 진단된 환자 43명 (aggressive periodontitis patients: AgP, 남자 30명, 여자 13명)을 대상으로 하였다. 모든 실험 대상자는 임상 실험에 대해 동의 하였고, 초진 시 전자 탐침(Florida Probe(R) Co. Gainesville, FL)을 이용하여 탐침 시 치주낭 깊이 (PPD), 임상부착수준 (CAL), 치태지수(PI), 탐침 후 출혈지수 (BOP)를 측정하였다. 또한 이들의 정맥혈에서 추출한 DNA를 PCR법, 전기영동법 등을 이용하여 $Fc{\gamma}RIIIa$, $Fc{\gamma}RIIIb$의 대립 유전자의 존재여부를 확인하였다. 이를 바탕으로 $Fc{\gamma}RIII$ 복합 유전형을 확인하여 각 군 간을 비교하였다. 연구 결과 1. $Fc{\gamma}RIIIa$에 대한 유전자다형성 연구 결과 대조군과 급진성 치주염 환자 군(AgP)사이에서는 대립 유전자 분포가 서로 유의성 있는 차이를 나타내었고 (P<0.05), $Fc{\gamma}RIIIb$에서는 유의성 있는 차이를 발견할 수 없었다. (P>0.05) 2. $Fc{\gamma}RIIIa$ 158F 대립형질이 급진성 치주염 환자에서 유의성 있게 많이 발견되어졌다. (P<0.05) 결론 이 연구를 통하여 $Fc{\gamma}RIIIa$ 유전자의 분석이 한국인의 급진성 치주염에 대한 감수성의 위험요소의 표지자로 활용할 수 있을 것으로 사료되며, 향 후 더 많은 환자를 대상으로 히는 추가 연구가 필요하다고 생각된다.

• BMB Reports
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• v.42 no.10
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• pp.636-641
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• 2009

The penetrating of monoclonal antibodies (mAbs) into solid tumor may be hampered by their large size. The antibody mimetics, composed of two complementarity-determining regions (CDRs) through a cognate framework region (FR), have been demonstrated to have the capacity to penetrate tumors superior to its parental intact IgG. In this study, we used CDR and FR sequences from the humanized anti-HER2 monoclonal antibody trastuzumab to design four antibody mimetics. Then these antibody mimetics were fused to human IgG Fc to generate mimetics-Fc small antibodies. One of the four mimetics-Fc antibodies binds well to HER2-overexpressing SK-BR3 cells and effectively inhibits the binding of trastuzumab. This mimetics-Fc, denoted as HMTI-Fc, was shown to be effective in mediating antibody-dependent cellular cytotoxicity and exhibit an antiproliferative effect in SK-BR3 cells. To our knowledge, the HMTI-Fc antibody shown here is the smallest fully functional antibody and may have a potential for treatment of cancer.