Previous studies have investigated the potential relationship between promoter polymorphism (-308, G/ A) of tumor necrosis factor (TNF)-α and various autoimmune diseases. However, results from published data were inconclusive. To verify relationship between TNF-α polymorphism (-308, G/A) and susceptibility to autoimmune diseases such as vitiligo, celiac disease, and rheumatoid arthritis, we have performed a metaanalysis with all relevant articles before October 2016. The electronic search of PubMed, google, and Embase databases was performed to identify eligible studies investigating the relationship of TNF-α polymorphism with autoimmune diseases including vitiligo, celiac disease, and rheumatoid arthritis. Genotype frequency data of TNF-α polymorphism (-308, G/A) were extracted and the meta analysis was performed by Comprehensive meta-analysis program with odds ratio (OR) and 95% confidence intervals (95% CI). Genotype models were applied with dominant and recessive models and allele model analyzed. The final analysis included 37 publication papers with a total of 6,102 autoimmune disease patients and 6,987 control subjects. In result, a statistical significant correlation between TNF-α polymorphism (-308, G/A) and susceptibility to autoimmune disease was not detected in our meta-analysis (p>0.05 in all models). Our results suggest that the TNF-α polymorphism might not be related to the development of autoimmune disease. If further results in larger studies would be accumulated in the future, this relationship would be clarified.

Tumor necrosis factor alpha (TNFα) is a multifunctional inflammatory cytokine that regulates various cellular and bio-logical processes. Increased levels of TNFα have been im-plicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (β2AR) in osteoblasts suppresses osteogenic activity. We previously reported that TNFα up- regulates β2AR expression in murine osteoblastic cells and that this modulation is associated with TNFα inhibition of osteoblast differentiation. In our present study, we explored whether TNFα induces β2AR expression in human osteo-blasts and then identified the downstream signaling path-way. Our results indicated that β2AR expression was increa-sed in Saos-2 and C2C12 cells by TNFα treatment, and that this increase was blocked by the inhibition of NF-κB acti-vation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-κB directly binds to its cog-nate elements on the β2AR promoter and thereby stimulates β2AR expression. These findings suggest that the activation of TNFα signaling in osteoblastic cells leads to an upregu-lation of β2AR and also that TNFα induces β2AR exp-ression in an NF-κB-dependent manner.

Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-α. The present study investigated the mechanisms involved in TNF-α production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-α. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-α by E. faecalis. In addition, antioxidant treatment reduced TNF-α production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-α expression by RAW 264.7 cells. Furthermore, activation of NF-κB and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-α in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-κB, and AP-1.

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of (30μM)SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration(30μM) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear factor-kB(NF-kB) determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce NF-kB and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

In odontogenic osteolytic lesions, the mechanism involved in inflammation 때d osteolysis is still under debate. We investigated the role 。OL-l ~ -1 ß, -4, -6, -8, TNF- a in the expansion of the odontogenic cysts, by using 50 cases of excised odontogenic cysts. The degrees of inflammation were graded into 2 groups and immunohistochernical stainings were performed, The cytoplasrnic reaction in squamous epithelial cells, stromal cells and infIitrating inflammatory cells was examined. The relationship between the expressions of IL-1 q -1 ß, -4, -6, -8, π-JF- aand the degree of inflammation and the correlation among them were analyzed. 까1e 비Stilαγtic expressions of IL-l ~ IL-l ß and TNF-awere 66.6%, 66.6% and 4O.00Al respeαively and the epithelial exp~않sions of IL-4, -6, -8 were 32.00Al, 38.00Al and 24.00Al respeαively. IL-4, -6 and 용 were positively stained in plasma cells in 38.00Al, endothelial cells in 40.00/0 and neutrophils in 24. 00Al respectively. The expresssion rate of IL-4 in plasma cells and IL-8 in epithelium and neutrophils were inα얹sed in ca않s with marked inflammation. 까1e exp!1않sion rate of IL-1 ßin 피해ocytes and IL-4 in plasma cells were positively correlated with the expæssion of TNF-1 ain histiocytes. π1e expression rate of anti-inflammatory cytokine IL-4 in the epithelium were correlated with the expression of IL-6 in the epithelium and endothelial cells. A1though statistically insi.맑표ìcant， the expression rate of IL-6 were decreased in cases with marked inflammation and nega디vely correlated with IL-8, the proinflammatory cytokine, and the expressions of IL-4 and IL-6 in the epithelium can be considered as inhibiting the inflammatory reaction. These results suggest that the expressions of IL-4 and IL-6 suppress and IL-8 stimulates the inflammatory reaction in Odontogenic Cysts.

급성전골수구성 백혈병(Acute promyelocytic leukemia, APL)은 혈액암의 일종으로 치료의 성적이 좋지 않 을 뿐 아니라 항암요법과 병행 하였을 경우 큰 효과를 보이는 것으로 알려져 있는 방사선 치료를 병행함에 도 불구하고 정상세포에도 작용하여 부작용을 초래한다. 본 연구에서는 이러한 부작용을 감소시키기 위하 여 감마선을 TNF-α와 같이 처리하였을 경우 정상세포와 암세포의 세포 죽음에 어떠한 영향을 미치는지 확 인하였다. HL-60 세포는 APL 세포주로서 사용하였고 DMSO를 처리하여 분화시킨 HL-60 세포는 정상과립 구의 성질을 나타내어 정상대조군으로 이용하였다. 그 결과 TNF-α와 함께 감마선을 처리한 HL-60 세포에 서만 세포독성효과를 나타내었고 세포자멸사를 유도하여 세포가 죽음에 이르게 하였다. 결론적으로 TNF-α 는 항암치료의 부작용을 없애기 위해 저농도 감마선 치료 시 함께 사용하여 암 세포의 제거를 증가시켜 암 의 치료효율을 높일 수 있는 유효물질로 사료된다.

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects on the water extracts of Artemisia princeps Pampanini (APP) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased PGE2 and TNF-α production. Consistent with these results, the protein and mRNA expression level of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by water extracts of APP in a dose-dependent manner. These results suggest that APP may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and Interferon-γ (IFN-γ) production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased IFN-γ and TNF-α production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

Naturally occurring substances are important biomedical resources with low toxicity and ethnopharmacology-based efficacy. Four out of 45 extracts (Celastrus orbiculatus, Cercis chinensis, Stephanadra incisa, and Weigela subsessilis) prepared from the bark of Korea Forest plants exhibited more than 50% of inhibition on TNF-α production in lipopolysaccharide (LPS)-activated RAW264.7 cells at 100 μg/ml. In particular, potential inhibitory components of 4 extracts showed more than 50% inhibition seemed to be concentrated in methylene chloride (MC) fraction from C. orbiculatus, in ethyl acetate (EtOAc) fraction from C. chinensis and in hexane (Hx) fraction from S. incisa, whereas inhibitory activities of W. subssilis were broadly seen in non-polar solvent fractions such as Hx, MC and EtOAc. Therefore, our results suggest that extracts from C. orbiculatus, C. chinensis, S. incisa and W. subsessilis may be developed as a therapeutic remedy against TNF-α-mediated diseases such as rheumatoid arthritis or further fractionated to isolate active components having antiTNF-α inhibitory activity.

Insulin과 tumor necrosis factor alpha(TNF-)에 의한 초기 배아 발생의 조절기작을 알아보고자 생쥐의 상실배를 대상으로 이들이 첨가된 배양액에서 형태발생, 세포증식을 조사하고, 포배에서 mitogen activated protein kinase(MAPK, ERK1/2)의 활성 변화에 미치는 영향을 조사하였다. Insulin은 상실배의 체외발생 및 포배내 할구 수를 대조군에 비해 유의하게 증가시켰으며, TNF-는 발생율을 유의

생쥐 착상전 초기배아에서 insulin과 tumor necrosis factor (TNF)에 의한 배아의 형태 발생, 세포증식, apoptosis 및 MAPK활성의 변화를 조사하였다. Insulin에 의해 형태발생 및 포배당 세포수가 증가되었으며 TNF 처리시 유의하게 감소하였다. TNT 전처리시 insulin에 의한 발생 및 세포수 증가 촉진효과가 상쇄되었으며 TNF는 배아내 caspase-3의 활성을 증가시켰다. Insulin은 단시간내에 포배에