• IMMUNE NETWORK
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• v.6 no.1
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• pp.6-12
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• 2006

Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

• Korean Journal of Animal Reproduction
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• v.22 no.2
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• pp.127-136
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• 1998

A chimeric gene comprising murine whey acidic protein(mWAP) and human growth hormone(hGH) was used to produce transgenic rats express hGH and secrete it into the blood. Two lines of transgenic rats carrying the mWAP/hGH construct were established; High line was characterized by relatively high levels of serum hGH, and low line had relatively low levels. The secretory profiles of rat GH(rGH) as well as hGH, the transgene product, were obtained in transgenic males and females of low line; both hGH and rGH serum levels were flattened with no episodic fluctuations, and the overall mean concentration of rGH was significantly lower than in normal littermates. Although the animals of High line showed an acceles, as assessed by vaginal opening and occurrence of first ovulation, advanced by 7∼8 days in both lines of animals. Accordingly, the body weight at puberty of low line transgenic females was much lower than that of normal littermates, indicating that continuous hGH expression could induce precocious puberty without enhancing the growth rate.

• BMB Reports
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• v.37 no.4
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• pp.474-479
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• 2004

The expressed sequence tag (EST) effort in Toxoplasma gondii has generated a substantial amount of gene information. To exploit this valuable resource, we chose to study tgd057, a novel gene identified by a large number of ESTs that otherwise show no significant match to known sequences in the database. Northern analysis showed that tgd057 is transcribed in this tachyzoite. The complete cDNA sequence of tgd057 is 1169 bp in length. Sequence analysis revealed that tgd057 possibly adopts two polyadenylation sites, utilizes the fourth in-frame ATG for translation initiation, and codes for a secretory protein. The longest open reading frame for the tgd057 gene was cloned and expressed as a recombinant protein (rd57) in Escherichia coli. Western analysis revealed that serum against rd57 recognized a molecule of ~21 kDa in the tachyzoite protein extract. This suggests that the tgd057 gene is expressed in vivo in the parasite.

• Natural Product Sciences
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• v.13 no.4
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• pp.283-288
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• 2007

Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.

• Parasites, Hosts and Diseases
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• v.56 no.6
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• pp.553-558
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• 2018

Pathogenic Acanthamoeba spp. cause granulomatous amoebic encephalitis and keratitis. Acanthamoeba keratitis (AK) is a rare but serious ocular infection that can result in permanent visual impairment or blindness. However, pathogenic factors of AK remain unclear and treatment for AK is arduous. Expression levels of proteins secreted into extracellular space were compared between A. castellanii pathogenic (ACP) and non-pathogenic strains. Two-dimensional polyacrylamide gel electrophoresis revealed 123 differentially expressed proteins, including 34 increased proteins, 7 qualitative increased proteins, 65 decreased proteins, and 17 qualitative decreased proteins in ACP strain. Twenty protein spots with greater than 5-fold increase in ACP strain were analyzed by liquid chromatography triple quadrupole mass spectrometry. These proteins showed similarity each to inosine-uridine preferring nucleoside hydrolase, carboxylesterase, oxygen-dependent choline dehydrogenase, periplasmic-binding protein proteinases and hypothetical proteins. These proteins expressed higher in ACP may provide some information to understand pathogenicity of Acanthamoeba.

• IMMUNE NETWORK
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• v.21 no.1
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• pp.3.1-3.16
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• 2021

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide since its outbreak in December 2019, and World Health Organization declared it as a pandemic on March 11, 2020. SARS-CoV-2 is highly contagious and is transmitted through airway epithelial cells as the first gateway. SARS-CoV-2 is detected by nasopharyngeal or oropharyngeal swab samples, and the viral load is significantly high in the upper respiratory tract. The host cellular receptors in airway epithelial cells, including angiotensin-converting enzyme 2 and transmembrane serine protease 2, have been identified by single-cell RNA sequencing or immunostaining. The expression levels of these molecules vary by type, function, and location of airway epithelial cells, such as ciliated cells, secretory cells, olfactory epithelial cells, and alveolar epithelial cells, as well as differ from host to host depending on age, sex, or comorbid diseases. Infected airway epithelial cells by SARS-CoV-2 in ex vivo experiments produce chemokines and cytokines to recruit inflammatory cells to target organs. Same as other viral infections, IFN signaling is a critical pathway for host defense. Various studies are underway to confirm the pathophysiological mechanisms of SARS-CoV-2 infection. Herein, we review cellular entry, host-viral interactions, immune responses to SARS-CoV-2 in airway epithelial cells. We also discuss therapeutic options related to epithelial immune reactions to SARS-CoV-2.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1513-1520
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• 2023

Kex2 protease (Kex2p) is a membrane-bound serine protease responsible for the proteolytic maturation of various secretory proteins by cleaving after dibasic residues in the late Golgi network. In this study, we present an application of Kex2p as an alternative endoprotease for the in vitro processing of recombinant fusion proteins produced by the yeast Saccharomyces cerevisiae. The proteins were expressed with a fusion partner connected by a Kex2p cleavage sequence for enhanced expression and easy purification. To avoid in vivo processing of fusion proteins by Kex2p during secretion and to guarantee efficient removal of the fusion partners by in vitro Kex2p processing, P₁', P₂', P₄, and P₃ sites of Kex2p cleavage sites were elaborately manipulated. The general use of Kex2p in recombinant protein production was confirmed using several recombinant proteins.

• Oncology Letters
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• v.18 no.1
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• pp.283-290
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• 2019

Wnt3a is a glycosylated ligand that activates the β-catenin-dependent signaling pathway. Wnt signaling is also important in the prostate tumor microenvironment, and Wnt proteins secreted by the tumor stroma promote resistance to therapy. Bioactive Wnt3a production requires a number of dedicated factors in the secretory cell, but their coordinated functions are not fully understood. We previously reported transmembrane protein 64 (Tmem64) as a novel regulator of the Wnt/β-catenin signaling pathway, which is correlated with β-catenin regulation. In the present study, the role of Tmem64 in prostate cancer cells was investigated by modulating Wnt3a secretion. Overexpression of Tmem64 inhibited Wnt3a secretion and Lef/Tcf-sensitive transcription. By contrast, a Tmem64 mutation deleting the protein's transmembrane region restored Wnt3a secretion. Notably, Tmem64 protein and mRNA in PC3 cells were significantly overexpressed compared with that observed in LNCaP and DU145 cells. In a mouse metastasis model intracardially injected with PC3 cells, Tmem64 expression was downregulated in the metastatic spine and mandible lesions compared with in the primary injection regions. However, Wnt3a was strongly expressed in the metastatic spine and mandible lesions. Collectively, these findings suggest that Tmem64 is involved in the metastatic progression of prostate cancer cells by regulating Wnt3a secretion.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.895-902
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• 2002

Monocytes and macrophages playa major role in defense mechanism of the host response to tumor, in part through the secretion of several potent products and macrophage cytokines. Monocytes and tissue macro phages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and tumor necrosis factor (TNF). Recent studies emphasizes that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. In this study, our work is directed toward studying the in vitro effects of Korean propolis on the ability to induce cellular and secretory responses in murine macrophage cell line, RAW 264.7. It was found that Water Extract of Korean Propolis (WEP) could activate macro phages by producing cytokines. The production of the macrophage cytokines, IL-1 and TNF-$\alpha$, by RAW 264.7 treated with WEP was examined from 2.5 $\mu\textrm{g}$/ml up to 25 $\mu\textrm{g}$/ml with dose dependent manner. Nitric oxide (NO) production was also increased when cells were exposed to combination of LPS and WEP from 2.5 $\mu\textrm{g}$/ml up to 25 $\mu\textrm{g}$/ml. At high dose of WEP (50 to 100 $\mu\textrm{g}$/ml) used to prescribe for anti-inflammatory and analgesic medicine showed inhibition of NO production in LPS-stimulated macrophage. Besides cytokine production, NO release, surface molecule expression and cell morphologic antigen expression were increased in response to the stimulation by WEP. These results suggested WEP may function through macrophage activation.

• Biomedical Science Letters
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• v.19 no.2
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• pp.158-163
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• 2013

Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.