• Journal of Periodontal and Implant Science
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• v.35 no.3
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• pp.799-811
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• 2005

This study was carried out to examine the potency of the three surface compo- nents from Porphyromonas gingivalis to stimulate the murine macrophage cell line RAW264.7 to synthesize the pro-inflammatory cytokine tumor necrosis factor alpha($TNF-{\alpha}$) and nitric oxide (NO). Lipopolysaccharide(LPS). lipid A-associated proteins(LAP) and saline-extractable surface -associated material(SAM) were isolated from P. gingivalis 381. $TNF-{\alpha}$ release into culture supernatants was determined by two-site ELISA. NO production was assayed by measuring the accumulation of nitrite in culture supernatants. Western blot analysis of iNOS and analysis of reverse transcription(RT)-PCR products were carried out. The surface components extracted from this bacterium were almost equally potent in stimulating release of $TNF-{\alpha}$ and NO by RAW264.7 cells. $TNF-{\alpha}$ that was being measured immunologically was due to activation of $TNF-{\alpha}$ gene transcription. The present study clearly shows that P. gingivalis surface components fully induced iNOS expression in RAW264.7 cells in the absence of other stimuli. The ability of P. gingivalis surface components to promote the production of $TNF-{\alpha}$ and NO may be important in the pathogenesis of inflammatory periodontal disease.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1379-1387
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• 2013

In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha ($TNF{\alpha}$) is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of $TNF{\alpha}$ gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p<0.001). In contrast to the genotypes A/A and A/G, cows with G/G genotype showed significant variability of milk and milk fat yield subject to sex of delivered calf. Milk yield and milk fat yield were significantly higher in the case of birth of a bull calf than with a heifer calf (p<0.03). The G allele frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77% in aboriginal Yakut cattle. Our results suggest that the $TNF{\alpha}$-824A/G gene polymorphism may have an influence on the reproductive efforts of cows over the course of lactation events depending on the sex of progeny. Allocation of resources according to sex of the calf allows optimizing the energy cost of lactation. This may be a probable reason for high G allele frequency in Yakut cattle breeding in extreme environmental conditions. Similarly, the dramatic fall in milk production after birth of a heifer calf increases the probability of culling for the cows with the G/G genotype in animal husbandry.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.5
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• pp.283-287
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• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.37-44
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• 2017

Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that $kr{\ddot{u}}ppel$-like factor 8 (KLF8) is essential for tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with $TNF{\alpha}$ significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by $TNF{\alpha}$ stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and $NF{\kappa}B$ binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, $SM22{\alpha}$, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and $SM22{\alpha}$ concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with $TNF{\alpha}$ enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and $SM22{\alpha}$, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.

• Journal of Genetic Medicine
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• v.6 no.2
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• pp.155-160
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• 2009

Purpose: Preeclampsia is a multisystem human pregnancy-specific disorder. The pathophysiology of preeclampsia is linked with over-stimulation of inflammatory cytokines by placental ischemia via reduced uterine perfusion pressure during pregnancy. Although an increase in tumor necrosis factor (TNF)-alpha has been reported in preeclamptic women, there is little evidence of a relationship between TNF-alpha gene variations and preeclampsia. In this study, we identified a single-nucleotide polymorphism (SNP), C-850T, in the TNF-alpha gene promoter region in Korean preeclamptic women and investigated the association between this SNP and the development of preeclampsia. Materials and Methods: This polymorphism was analyzed in peripheral blood samples from 198 preeclamptic pregnancies and 194 normotensive pregnancies using a SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results: Genotypes and allele frequencies for C-850T did not differ between preeclamptic and normotensive pregnancies. The distributions of genotypes (CC, CT and TT) were 74.3%, 22.2% and 3.5%, respectively, in preeclamptic pregnancies, and 71.6%, 25.8% and 2.6%, respectively, in normotensive pregnancies. The frequencies of the C and T alleles were 0.85 and 0.15 in preeclamptic pregnancies and 0.84 and 0.16 in normotensive pregnancies, respectively. There was no increased risk of preeclampsia in subjects with the CT (OR, 0.83; P=0.44) or TT genotypes (OR, 1.32; P=0.64). Conclusion: We found no differences in the genotypes or allele frequencies of the TNF-alpha gene polymorphism between preeclamptic and normotensive pregnancies. This study suggests that the TNF-alpha gene polymorphism may be not associated with the development of preeclampsia in pregnant Korean women.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9177-9183
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• 2014

Polymorphisms of inflammation-related genes have been found to be associated with non-Hodgkin lymphoma (NHL) or some of its subtypes, but only a few relevant data have been reported in China. In this study, the Snapshot method was used to assess genetic variation; a total of 14 single nucleotide polymorphisms (SNPs) for 6 inflammatory factors in 157 NHL cases (64 Uygur ethnic subjects, 93 Han Chinese) and 435 controls (231 Uygur and 204 Han Chinese) were studied from the Xinjiang province of China. Haplotype distribution was estimated using PHASE 2.3 software. Statistical differences in the genotype and haplotype frequencies between case and control groups were also considered and estimated. For the Han population, the geneotype distributions for TNF-${\alpha}rs1800629$, TNF-${\alpha}rs1800630$, IL-6 rs1800795, IL-6 rs1800797, NF-KB1 rs1585215 and TLR-4 rs4986790 showed significant differences between the case and control groups (p<0.05). The TNF-${\alpha}$ gene frequencies of ACG and CCA haplotypes in the cases were higher than in the controls (OR=2.45, 95% CI: 1.55-3.89, p=0.0002, OR=2.53, 95% CI: 1.10-5.80, p=0.029, respectively), and the same findings were detected for TNF-${\beta}$ gene CA haplotype (OR=1.87, 95% CI: 1.21-2.90, p=0.0054). However, for the Uygur population, no such significant differences were detected within the gene-type distribution of the 14 SNPs. The TNF-${\alpha}$ gene frequency of the CCA haplotype between the two groups (OR=1.98, 95% CI: 1.11-3.51, p=0.021) revealed a statistically significant difference. Our results showed that polymorphic variations of inflammation-related genes could be important to the NHL etiology of the Han population, and that these may only have limited influence on the Uygur population.

• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.298-305
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• 2018

Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramembrane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha ($TNF-{\alpha}$) converting enzyme, which is the molecule responsible for the release of $TNF-{\alpha}$. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of $TNF-{\alpha}$ release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative $TNF-{\alpha}$ related disease, was induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity of the CIA was measured by traditional clinical scores and histopathological analysis of hind limb joints. A rota-rod test and grip strength test were employed to evaluate the severity of CIA based on losses of physical functions. The results indicated that Rhbdf2 mutant mice showed clear alleviation of the clinical severity of CIA as demonstrated by the significantly lower severity indexes. Moreover, a grip strength test was shown to be useful for the evaluation of physical functional losses by CIA. Overall, the results showed that the Rhbdf2 gene has a significant effect on the induction of CIA, which is related to $TNF-{\alpha}$.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.62-67
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• 2004

Trauma remains one of the important sources leading to systemic inflammatory response anti sub-sequent multiple organ failure. Although hepatic microvascular dysfunction occurs during trauma, the mechanism responsible remains unclear. The aim of this study was to investigate the effect of trauma on hepatic vascular stress gene expression. Femur fracture (EFx) was induced by torsion to the femur at midshaft. Liver samples were taken for RT-PCR analysis of mRNA for gtenes of interest: endothelin-1 (ET-1), its receptors $ET_A$ and $ET_B$, nitric oxide synthases (iNOS and eNOS), cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and tumor necrosis tactor-${\alpha}$ (TNF-${\alpha}$). The expression of ET-1 mRNA was significantly increased by FFx. Expression of mRNA in FFx group showed no change in $ET_A$, $ET_B$, iNOS and HO-1 and showed a slight increase of 2.2-fold and 2.7-fold for eNOS tll1d COX-2, respectively. The level of TNF-${\alpha}$ mRNA significantly increased in FFx group. In conclusion, mild trauma alone causes little change in expression of vasoactive mediators.

• International Journal of Oral Biology
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• v.44 no.4
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• pp.182-190
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• 2019

Periodontitis is an inflammatory disease of the supportive tissues surrounding the teeth, and is characterized by irreversible destruction of the gingiva, periodontal ligament (PDL), and alveolar bone, which results in the loss of teeth. In the present study, we elucidated the correlation between periodontitis and apelin (APLN), an adipokine and a regulatory peptide, respectively, which are involved in inflammation and bone remodeling. The expression of APLN is negatively correlated with periodontitis progression in gingival tissue. In addition, treatment with TNF-α downregulated the expression of APLN in PDL cells and gingival fibroblasts, indicating the protective role played by APLN against periodontitis progression. The overexpression of APLN or treatment with exogenous APLN suppressed the TNF-α-mediated catabolic gene expression of MMP1, IL6, and PTGS2 in PDL cells. Moreover, the inhibition of the APLNA-PJ axis by ML221, an APJ inhibitor, induced catabolic gene expression in PDL cells. Thus, the results of this study provided evidence to support APLN as a regulatory factor of the inflammatory response during periodontitis.

• Journal of Acupuncture Research
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• v.18 no.4
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• pp.125-142
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• 2001

Objective : The purpose of this study is to observe the effect of Aqua-acupuncture with Stephania Tetrandra Solution (ST-AS) on arthritis. Methods : The author performde several experimental items : that isgene expression and secretion of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, MMP-2, production of ROS, paw thickness, DTH, weight of spleen, expression of CD4+, CD8+, CD19+ in the spleen, production of IL-6, TNF-${\alpha}$, examination of histology. Results : The obstain results are summarized as follows. 1. IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene expression of hFLS were significantly inhibited in treatmentgroup, and gene expression of MMP-2 was not inhibited in treatmentgroup. 2. The secretion amount of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ were significantly inhibited in treatmentgroup. 3. Expression of P-38 MAP kinase and production of ROS were inhibited in treatmentgroup. 4. Treatmentgroup were significantly inhibited the incidence of arthritis, hind paw edema, the index of arthritis and DTH of CIA (collagen II-induced arthritis) mice. 5. Treatmentgroup were significantly decreased splenetic weight and the number of CD4+, CD8+, CD19+ activated cells and secretion aroout of IL-6, TNF-${\alpha}$ of CIA (collagen II-induced arthritis) mice.. 6. Treatmentgroup were expressed form of new bone, synoviumin, new margine in histology imperison to controlgroup. Conclusions : Taking all these observations into account, ST-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.