• Molecules and Cells
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• 제39권5호
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• pp.395-402
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• 2016

Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated regulatory networks underlying its roles during development. However, identification of these genes remains difficult due to intrinsic factors of Hoxc8, such as low DNA binding specificity, context-dependent regulation, and unknown cofactors. Therefore, as an alternative, the present study attempted to test whether the roles of Hoxc8 could be inferred by simply analyzing genes frequently coexpressed with Hoxc8, and whether these genes include putative target genes. Using archived gene expression datasets in which Hoxc8 was differentially expressed, we identified a total of 567 genes that were positively coexpressed with Hoxc8 in at least four out of eight datasets. Among these, 23 genes were coexpressed in six datasets. Gene sets associated with extracellular matrix and cell adhesion were most significantly enriched, followed by gene sets for skeletal system development, morphogenesis, cell motility, and transcriptional regulation. In particular, transcriptional regulators, including paralogs of Hoxc8, known Hox co-factors, and transcriptional remodeling factors were enriched. We randomly selected Adam19, Ptpn13, Prkd1, Tgfbi, and Aldh1a3, and validated their coexpression in mouse embryonic tissues and cell lines following $TGF-{\beta}2$ treatment or ectopic Hoxc8 expression. Except for Aldh1a3, all genes showed concordant expression with that of Hoxc8, suggesting that the coexpressed genes might include direct or indirect target genes. Collectively, we suggest that the coexpressed genes provide a resource for constructing Hoxc8-mediated regulatory networks.

• IMMUNE NETWORK
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• 제7권1호
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권5호
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• pp.420-424
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• 2011

Allomatrix (Wright Medical Tech, Inc., Arlington, Tenn, USA), is a newly designed, injectable putty with a reliable demineralized bone matrix (DBM), derived from human bone. The compound contains 86% DBM and other bone growth factors such as bone morphogenic protein (BMP)-2, BMP-4, insulin-like growth factor (IGF)-1, and transforming growth factor (TGF)-${\beta}1$. It has excellent osteoinduction abilities. In addition, DBM is known to have osteoconduction capacity as a scaffold due to its collagen matrix. This product contains a powder, which is a mix of DBM and surgical grade calcium sulfate as a carrier. A practitioner can blend the powder with calcium sulfate solution, making a putty-type material which has the advantages of ease of handling, better fixation, and no need for a membrane, because it can function as membrane itself. This study reports the clinical and radiographic results of various guided bone regeneration cases using Allomatrix, demonstrating its strong potential as a graft material.

• Fisheries and Aquatic Sciences
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• 제18권3호
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• pp.273-281
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• 2015

The follistatin (FST) gene encodes a monomeric glycoprotein that plays a role in binding and inhibiting the functions of members of the transforming growth factor (TGF)-${\beta}$ superfamily. Thus, FST facilitates a wide variety of functions, ranging from muscle growth, to inflammation and immunity. In this study, we sought to characterize an FST counterpart, RbFST, which was identified from rock bream Oplegnathus fasciatus. The RbFST cDNA sequence (2,419 bp) contains a 933-bp open reading frame (ORF) that encodes a putative amino acid sequence for RbFST (35 kDa). The putative amino acid sequence contains a Kazal-type serine protease inhibitor domain (51-98 residues) and an EF-hand, calcium-binding domain (191-226 residues). Additionally, this sequence shares a high identity (98.7%) with the Siniperca chuatsi FST sequence, with which it also has the closest evolutionary relationship according to a phylogenetic study. Omnipresent distribution of RbFST transcripts were detected in the gill, liver, spleen, head kidney, kidney, skin, muscle, heart, brain, and intestine of healthy animals, with significantly higher expression levels in the heart, followed by the liver tissue. Under pathogenic stress caused by two bacterial pathogens, Streptococcus iniae and Edwardsiella tarda, RbFST transcription was found to be significantly up-regulated. Altogether, our findings suggest the putative role of RbFST in immune related responses against pathogenic infections, further prefiguring its significance in rock bream physiology.

• IMMUNE NETWORK
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• 제12권1호
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• pp.27-32
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• 2012

Background: Toll-like receptors (TLRs) have been extensively studied in recent years. However, functions of these molecules in murine B cell biology are largely unknown. A TLR4 stimulant, LPS is well known as a powerful polyclonal activator for murine B cells. Methods: In this study, we explored the effect of a murine TLR9 stimulant, M6-395 (a synthetic CpG ODNs) on B cell proliferation and Ig production. Results: First, M6-395 was much more potent than LPS in augmenting B cell proliferation. As for Ig expression, M6-395 facilitated the expression of both TGF-${\beta}1$-induced germ line transcript ${\alpha}$ ($GLT{\alpha}$) and IL-4-induced $GLT{\gamma}1$ as levels as those by LPS and Pam3CSK4 (TLR1/2 agonist) : a certain Ig GLT expression is regarded as an indicative of the corresponding isotype switching recombination. However, IgA and IgG1 secretion patterns were quite different--these Ig isotype secretions by M6-395 were much less than those by LPS and Pam3CSK4. Moreover, the increase of IgA and IgG1 production by LPS and Pam3CSK4 was virtually abrogated by M6-395. The same was true for the secretion of IgG3. We found that this unexpected phenomena provoked by M6-395 is attributed, at least in part, to its excessive mitogenic nature. Conclusion: Taken together, these results suggest that M6-395 can act as a murine polyclonal activator but its strong mitogenic activity is unfavorable to Ig isotype switching.

• 대한본초학회지
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• 제20권4호
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• pp.141-149
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• 2005

In order to investigate the immunomodulational effects of Lonicerae Caulis et Folium, the author measured cytokines production(IL-10, IL-12(P35), IL12(P40), $IFN-{\gamma}$) in mice splenocytes. The results were obtained as follows : 1. The water extract of Lonicerae Caulis et Folium significantly enhanced the gene expression of IL-12(P35), IL-12(P40), but reduced the gene expression of IL-10, $IFN-{\gamma}$. 2. In water fraction and ethyl acetate fraction, the gene expression of IL-12(P35), $IFN-{\gamma}$ was significantly increased and that of IL-12(P40), IL-10 was decreased. The above results demonstrate that Lonicerae Caulis et Folium has enhancing immune activity by upregulation of these cytokines. Therefore, if we make the relationship between these cytokines(IL-10, IL-12, $IFN-{\gamma}$) besides IL-1, IL-4, IL-6, $TNF-{\alpha}$, IL-8, $TGF-{\beta}$ and so on which concerned the immunopotentiation, the immunopotentiational mechanism of Lonicerae Caulis et Folium will be shown clearly.

• BMB Reports
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• 제43권8호
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• pp.554-560
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• 2010

Smad4 is involved in cancer progression and metastasis. Using a pair of human syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM) metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for ovarian cancer. Re-expression of Smad4 decreased the migration ability and inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion capacity for HO-8910PM. The stable expression of Smad4 increased the expression of E-cadherin, reduced the expression of plasminogen activator inhibitor-1 (PAI-1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human ovarian cancer cell metastasis potential through its effect on the expressions of PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4 might suppress the invasion and metastasis of human ovarian tumor cells through a TGF-$\beta$/Smad-mediated pathway.

• 대한의생명과학회지
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• 제21권2호
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• pp.122-125
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• 2015

House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

• 대한한방내과학회지
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• 제27권1호
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• pp.208-220
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• 2006

Objective: Eosinophils are typically characterized by a bilobar nucleus with highly condensed chromatin and cytoplasm containing two major types of granules, specific and primary granules, and lipid bodies. The role of inflammation in asthma and other allergic diseases of the airways is widely appreciated, and airway inflammation is now included as a defining feature of asthma. The importance of the presence of eosinophils in the airways of patients with fetal asthma has long been recognized, but the mechanism by which these cells are recruited and retained in the lungs are only now being elucidated. Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Methods : Water extracts of Armeniacae Amarum Semen(AAS) and pulmonary epithelial cell lines A549(alveolar typeII epithelial cells) and human eosinophils were used. Cytotoxic effects of AAS and MIS assay were estimated, as well as the effects of AAS on chemokines from prestimulated A549 cells by sandwich ELISA and RI-PCR. Chemotaxis assay was conducted on prestimulated eosinophils treated with AAS. Results : In this study it is demonstrated that $TGF-{\alpha}$, IL-4 and $IL-1{\beta}$ induced the accumulation of chemokine mRNAs in the alveolar epithelial cell lines A549 in dose-dependent manner. Eotaxin and IL-8 were inhibited by AAS in dose-dependent manner(p<0.05). Eosinophil migration was inhibited at high concentrations of AAS(p<0.05). Conculusions : These findings are indicative of suppression of eotaxin and IL-8, and suggest that this is accomplished through AAS treatment. This raises the possibility that AAS is of therapeutic value in diseases such as asthma.

• 대한한방내과학회지
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• 제30권2호
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• pp.365-374
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• 2009

Objectives : The aim of this study was to investigate the effects of Gamisaenggan-tang on high fat diet induced nonalcoholic fatty liver disease. Methods: Rats were randomly divided into four groups. The Normal group was fed a solid diet containing 10% fat. The Gamisaenggan-tang (GS) group was fed a solid diet containing 10% fat and Gamisaenggan-tang (90mg/100g body weight). The Control group was fed a solid diet containing 60% fat. The HFD-Gamisaenggan-tang (HFD-GS) group was fed a solid diet containing 60% fat and Gamisaenggan-tang (90mg/100g body weight). Six weeks later, rats body weight, liver weight, serum ALT, GGT, ALP levels were measured. Histological findings (Oil red O staining), hepatic triglyceride, TNF-${\alpha}$, and TGF-${\beta}$ levels in the liver tissue were studied. Results: Average body weight of the HFD-GS group was significantly less than that of the Control group. There were no significant liver weight differences among each group. The GGT levels of the HFD-GS group were significantly less than those of the Control group. However, there were no significant differences in the ALT or ALP levels among the groups. TNF-${\alpha}$ protein production assessed by western blot analysis was reduced by Gamisaenggan-tang. Greater fat accumulation was observed in the liver tissue of the Control group than in the HFD-GS group, which means the Gamisaenggan-tang has an inhibitory effect on the accumulation of fat in the liver. Conclusion : The results suggest that Gamisaenggan-tang can be potential candidate for the treatment of nonalcoholic fatty liver disease in clinics.