Inflammatory bowel disease (IBD) is a chronic condition characterized by continuous inflammation of the gastrointestinal tract that varies in intensity over time. IBD is caused by several factors including aberrant gut flora, immunological dysregulation, altered environmental conditions, and genetic variations. However, the pathogenesis of IBD remains unclear. Studies have indicated that an imbalance between T helper 17 (Th17) and regulatory T (Treg) cells contributes significantly to the development of IBD. Intestinal Tregs suppress inflammation and are critical for maintaining tissue homeostasis. Th17 cells are known to play an important role in the development and pathogenesis of IBD and provide non-inflammatory support for the integrity of the intestinal barrier against bacterial and fungal infections. Therefore, the Th17/Treg cell balance is crucial in the pathogenesis of IBD and gut integrity. The microenvironment of the intestinal mucosal immunity is regulated by the secretion of cytokines associated with Th17 cells and Tregs. Several studies have indicated that the gut bacteria contribute to the control of the immune milieu and play a key role in the regulation of Th17 cell development. Intestinal bacteria and cytokines control Th17 cell development. Th17 cells secrete cytokines that regulate the immune microenvironment in the gut mucosa. This review provides an overview of Th17 cells and examines the strategies for treating patients with IBD using Th17 cell-targeted drugs.

High levels of proinflammatory cytokines have been observed in obese pregnancies. Obesity during pregnancy may increase the risk of various pregnancyrelated complications, with pathogenesis resulting from excessive inflammation. Palmitic acid (PA) is a saturated fatty acid that circulates in high levels in obese women. In our previous study, we found that PA inhibited the proliferation of trophoblasts developing into the placenta, induced apoptosis, and regulated the number of cleaved halves derived from transfer RNAs (tRNAs). However, it is not known how the expression of tRNA-derived stress-induced RNAs (tiRNAs) changes in response to PA treatment at concentrations that induce inflammation in human trophoblasts. We selected concentrations that did not affect cell viability after dose-dependent treatment of HTR8/SVneo cells, a human trophoblast cell line. PA (200 μM) did not affect the expression of apoptotic proteins in HTR8/SVneo cells. PA significantly increased the expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 , and tumor necrosis factor (TNF)-α . In addition, 200 μM PA significantly increased the expression of tiRNAs compared to 800 μM PA treatment. These results suggest that PA impairs placental development during early pregnancy by inducing an inflammatory response in human trophoblasts. In addition, this study provides a basis for further research on the association between PA-induced inflammation and tiRNA generation.

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy and an increasing global public health problem. OSCC frequently invades the jaw bone. OSCC-induced bone invasion has a significant impact on tumor stage, treatment selection, patient outcome, and quality of life. A number of studies have shown that osteoclastmediated bone resorption is a major step in the progression of bone invasion by OSCC; however, the molecular mechanisms involved in OSCC bone invasion are not yet clear. In this review, we present the clinical types of OSCC bone invasion and summarize the role of key molecules, including proteases, cytokines, and growth factors, in the sequential process of bone invasion. A better understanding of bone invasion will facilitate the discovery of molecular targets for early detection and treatment of OSCC bone invasion.

Bropirimine, a class of antineoplastic agents, is known as one of the potent immunomodulators and is currently under clinical development for the treatment of cancer. However, the effect of bropirimine on the cow remains unknown as a therapeutics agent. In this experiment, the effect of bropirimine in the peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) or concanavalin-A (Con-A) was examined. Jugular venous blood was collected from Korean Hanwoo calves and PBMCs were isolated. It was used to study the effect of bropirimine upon stimulation with LPS or Con-A for 72 hours. The expression pro-inflammatory cytokines like Tumor Necrosis Factor α (TNF-α) and Interferon γ (IFN-γ) were confirmed. Bropirimine significantly inhibited LPS- or Con-A-induced TNF-α and Con-A-induced IFN-γ in dose-dependent manner. Furthermore, Bropirimine inhibited TNF-α and Con-A mRNA expression at the transcription level. These results clearly indicated that bropirimine inhibited LPS or Con-A stimulated up-regulation of proinflammatory cytokines in a dose-dependent manner without conspicuous cytotoxicity. The bropirimine has potential to protect cow from LPS or Con-A induced endotoxin shock, possibly through inhibition of the production of proinflammatory cytokines. It suggesting that bropirimine may be a novel therapeutic agent for the prevention of inflammatory diseases. This result revealed specific features of the immune responses depending on the bropirimine compound and would help to knowledge of bovine immunity.

혈청을 이용한 분석은 다양한 질병 진단의 지표로 이용 된다. 혈청의 분리 방법, 저장시간 및 온도에서 부적절한 혈액 처리는 사이토카인의 농도와 생화학 검사결과에 영 향을 줄 수 있다. 본 연구에서는 한우를 공시하여 혈청 분 리 시기, 저장 시간과 온도가 사이토카인 및 생화학 검사 결과에 미치는 영향을 조사 하였다. 혈액은 경정맥에서 채 취하여, 26±3℃에서 1~2시간 방치 후 분리조건을 다음과 같이 4개의 그룹 (a-d)으로 나뉘어 진행하였다. a) 혈청 분 리하여 보관(대조구), b) 혈청분리 후 아이스박스 2시간 방 치 후 보관, c) 아이스박스 2시간 방치 후 혈청분리, d) 24 시간 4℃ 방치 후 혈청분리, 이러한 조건으로 분리된 혈청 은 분석 전까지 –70℃ 보관 하였다. 혈청 분리시기, 아이스 박스 또는 4℃ 저장 시간 및 온도에 따라 IFN-γ는 유의적 인 차이를 보이지 않았고, TNF-α의 농도는 그룹 a-c에 비 해 그룹 d에서 유의적(p<0.05)으로 낮아졌다. 또한 albumin, total protein의 농도는 그룹 a보다 d에서 유의적 (p<0.01)으로 높았고, magnesium, calcium에서도 유사한 결과를 보였다(p<0.05). 그러나 G-GTP의 경우 다른 그룹에 비해 그룹 d에서 유의적(p<0.05)으로 가장 낮아졌다. 그러 므로 시료채취 시 농가와 실험실의 거리를 고려하여 온도와 저장시간이 혈청 내 사이토카인 및 생화학 농도에 미치 는 영향을 최소화 하여 연구 수행을 진행해야 될 것으로 사료된다.

Many kinds of medicinal herbs have been used to treat inflammation in Oriental medicine. However, there few studies have investigated the anti-inflammatory activity of medicinal herbs. In this study, we used mouse bone marrow cells (BMs) treated with lipopolysaccharide (LPS), a simulator of osteomyelitis, to screen medicinal herbs having anti-inflammatory activity. Specifically, we investigated the activity of an extract of Rhus chinensis (RC) using metabolic activity and cytokine production of the BMs treated with LPS and RC. The metabolic activity of BMs was measured using Cell Counting Kit-8® solution. RC decreased the metabolic activity of LPS-treated BMs. A viability assay using trypan blue solution demonstrated that RC marginally decreased the viability of LPS-treated BMs. Flow cytometry analysis revealed that RC decreased the mitochondrial membrane potential of BMs, regardless of LPS treatment. To investigate the anti-inflammatory activity of RC, we measured the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 in BMs. LPS increased the production of both cytokines in BMs. Interestingly, RC induced a greater increase in IL-10 than TNF-alpha in LPS-treated BMs. Taken together, RC decreased metabolic activity and modulated the production of inflammation-related cytokines in LPS-treated BMs. These findings suggest that RC can be used as a medicinal herb with anti-inflammatory activity.

Pro-inflammatory cytokines, interleukin-1β (IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

최근 알로에 베라 섭취에 의한 독성 간염이 보고되고 있으나, 아직까지 알로에 베라의 간에 대한 염증 효과가 명확히 밝혀지지 않았다. 본 연구는 알로에 베라 에탄올 추출물이 간세포의 염증 발현에 미치는 영향과 그 기전을 밝히기 위해 수행되었다. 0.001~100 μg/mL의 알로에 베라 추출물을 HepG2세포에 처리하여 MTT assay를 시행한 결과, 모든 농도에서 세포사멸이 유도되지 않았다. 그러나 모든 농도에서 알로에 베라 추출물은 염증성 사이토카인인 IL-8의 분비를 15.7~25.8%까지 유의적으로 증가시켰다(p<0.05). 또 다른 사이토카인인 M-CSF도 알로에 베라 추출물에 의해 36.3~61.5%까지 유의적으로 분비가 증가되었다(p<0.05). 본 연구 결과는 알로에 베라 추출물이 IL-8과 M-CSF와 같은 염증성 사이토카인 분비기전에 의해 간에 염증을 유발할 수 있음을 보여준다. 또한 알로에 추출물에 의해 유발될 수 있는 간염기전을 제시함으로써, 향후 수행될 추가 실험을 위한 기초 자료로 그 가치가 높을 것으로 사료된다.

Haemaphysalis longicornis (Hl) as members of the ixodid tick inhabits lots of grass thicket of field and mountain. Ticks are blood-feeding ectoparasites that can mediate a variety of diseases to human and animals, causing Lyme disease, Rocky Mountain spotted fever, and human monocytic ehrlichiosis. Particularly, ticks can trigger an inflammatory response representing symptoms about swelling and itching in human. The aim of this study is to investigate the effect of H. longicornis extract (HlE) on production of inflammatory cytokines and their mRNA in human monocytic THP-1 cells. In a time- and dose-dependent manner, human monocytic THP-1 cells was treated with HlE. Supernatants were analyzed for the production of cytokines using enzyme-linked immunosorbent assay (ELISA). mRNA level in the culture cells was measured by a reverse transcriptase-polymerase chain reaction (RT-PCR). As a result of this study, HlE significantly induced secretion of IL-6, IL-8, and MCP-1 in THP-1 cells. These results suggest that HlE increase the release of proteins and mRNAs level of inflammatory cytokines in THP-1 cells. HlE may play a role in contributing to inflammatory diseases through stimulation of immune cells. Further research of H. longicornis is needed to better understand the elucidation of the pathogenic mechanism.

Tyrophagus putrescentiae (Tp) as a storage mite inhabitats in stored grains, hay, and straw at agricultural areas. T. putrescentiae stimulates an immune response and triggers inflammatory cytokines release, and thus it is a source of allergen that sensitize and induce allergic reactions. Also, T. putrescentiae has been reported to cause asthma and atopic disease by cross-reactivity with Dermatophagoides pteronyssinus (Dp). The study on T. putrescentiae in human monocytic THP-1 cells is not enough to understand cytokine expression and pathological mechanisms. The aim of this study is to investigate the effect of T. putrescentiae extract (TpE) on production of inflammatory cytokines and expression of mRNA level in THP-1 cells. THP-1 cells are treated with TpE and supernatants were analyzed for the production of cytokines using enzyme-linked immunosorbent assay (ELISA). mRNA level in the culture cells was measured by a reverse transcriptase-polymerase chain reaction (RT-PCR). As a result of this study, TpE significantly induced secretion of interleukin-6, interleukin-8, and monocyte chemotactic protein-1 (MCP-1) in THP-1 cells in time- and dose-dependent manner. These results suggest that TpE may play a role in contributing to inflammatory disease through stimulation of immune cell. Further research of T. putrescentiae is needed to understand the elucidation of the pathogenic mechanism.

Inflammation functions as a double-edged sword against external stimulus. For instance, inflammation can have anti-cancer effect and simultaneously can play cancer-promoting factors. Recent studies have shown that cytokine plays an important role in tumor biology by influencing tumor growth, invasion and metastasis. We classify these cytokines by cancer type and review current knowledge of cytokines in terms of carcinogenesis. Here, we also focus on whether cytokines can act as biomarkers for early detection of oral squamous cell carcinoma (OSCC). This review will provide basis for further approach to study the role of cytokines in carcinogenesis and evaluating the possibilities of cytokines as biomarkers for cancer detection

Human gingival fibroblasts (hGFs) were reported to play an important role in inflammatory reactions to lipopolysaccharide (LPS) from P.gingivalis in the periodontal connective tissue. Although the biostimulatory effects of hyperbaric oxygen therapy, such as anti-inflammatory activity, have been reported, the pathological mechanism is not completely understood. This study examined the changes in the inflammatory cytokine profiles, which are produced after exposure to hyperbaric oxygen in P.gingivalis LPS-treated human gingival fibroblasts, and subsequently to examine the mitogen activated protein kinase (MAPK) pathway involved in cytokine production. Gingival fibroblasts with or without P.gingivalis LPS were exposed to hyperbaric oxygen, and the cytokine profiles in the supernatant were observed using a human inflammation antibody array. The expression of cyclooxyginase-2 (COX-2) protein, phosphorylation of extracellular signal-regulated kinase (ERK1/2), p38, and c-Jun-N-terminal kinase (JNK) MAPK by western blot analysis, and the amount of prostaglandin E2 (PGE2) in the supernatant by an enzyme-linked immunoassay were determined. COX-2 protein expression and PGE2productionwereincreasedsignificantlyintheP. gingivalis LPS-treated group, and were decreased by treating P. gingivalis LPS with hyperbaric oxygen. Treatment of P. gingivalis LPS in the gingival fibroblasts led an increase in the amount of pro-inflammatory-related cytokines interleukin-6 (IL-6) and IL-8 released, whereas hyperbaric oxygen inhibits the irrelease. Ananalysis of the MAPK signal transduction showed that hyperbaric oxygen induced a significant decrease in the level of P38 phosphorylation regardless of the presence or absence of LPS. In addition, hyperbaric oxygen promoted JNK phosphorylation, significantly in the presence of LPS. Hyperbaric oxygen can inhibit pro-inflammatory cytokines and mediate the MAPK signal pathway, and appears to be useful as an anti-inflammatory tool.

Porphyromonas gingivalis is a major etiologic agent of chronic periodontitis and cytokines produced by macrophages play important roles in the pathogenesis of periodontal diseases. In this study we investigated the cytokine response of phorbol myristate acetatedifferentiated THP-1 cells exposed to P. gingivalis. Compared with the prominent cell wall components of P. gingivalis (lipopolysaccharide and the major fimbrial protein FimA), live P. gingivalis stimulated much higher levels of cytokine production. In addition, whereas low multiplicity of infection challenges (MOI=10) of P. gingivalis 381 stimulated high levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, high dose challenges with this bacterium (MOI = 100) resulted in a substantially diminished production of MCP-1 and IL-6. Moreover, high MOI P. gingivalis challenges achieved only low levels of induction of MCP-1 and IL-6 mRNA. The decreased production of MCP-1 and IL-6 appeared to be mediated by P. gingivalis proteases, because high MOI challenges with congenic protease mutant strains of this microorganism (MT10 and MT10W) did not result in a diminished production of MCP-1 and IL-6. Similar to its protease mutant strains, leupeptin (a protease inhibitor)- treated P. gingivalis at high doses induced high levels of MCP-1 production. To examine the mechanisms underlying the diminished production of MCP-1 by P. gingivalis proteases, the activation of mitogen-activated protein (MAP) kinases and NF-xB was compared between the 381 and MT10W strains. Whilst high doses of both 381 and MT10W similarly activated the three members of the MAP kinase family, the DNA binding activity of NF-xB, as revealed by gel shift assays, was greatly increased only by MT10W. Taken together, our data indicate that P. gingivalis stimulates the production of high levels of TNF-α, IL-1β, IL-6, and MCP-1 but that high dose challenges with this bacterium result in a diminished production of MCP-1 and IL-6 via the protease-mediated suppression of NF-B activation in THP-1 macrophagic cells.

Ocjective : Sabaeksan has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in korea. Methods : To investigate the biological effect of Sabaeksan, the author examined cytotoxicity and inflammatory cytokines secretion with human leukemic mast cell line, HMC-1. HMC-1 was stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. Sabaeksan by itself had no effect on viability of HMC-1. Result : The effects of Sabaeksan on the secretion of tumor necrosis factor-alpha (TNF- α) and interleukin (IL)-6 from HMC-1 were evaluated with enzyme-linked immunosorbent assay. Sabaeksan (1 ㎎/㎖) inhibited PMA plus A23187-stimulated TNF-α and IL-6 secretion, by 43.86 ± 5.26%, 56.39 ± 3.65%, respectively. Sabaeksan also inhibited the NF-κB (p50/p65) expression. Conclusion : Taken together, these results suggest that Sabaeksan inhibit the production of inflammatory cytokines in HMC-1 cells through blockade of NF-κB activation.

To investigate the effects of bacterial endotoxin on lipids and cytokines, and to explain the relationships between their changes, we carried out this study using experimentally Escherichia coli (E. coli) endotoxin-induced septicemic rabbits. The triglyceride and cholesterol concentrations in endotoxin groups were generally high (p$lt;0.01 or 0.05) at all sampling time points (from 3hr to 24 hr), while phospholipid concentrations in endotoxin groups elevated in dose-dependent fashion at 3hr and 6hr after endotoxin injection compared to control group (p$lt;0.05). There were significant negative correlations between lipids changes and cytokines (TNF-α and IL-1β) each other (p$lt;0.05), and endotoxic rabbits having higher triglyceride of cholesterol levels shown relatively better conditions compared with others. As a result, the alterations in the lipid compositions caused by endotoxin may imply an active exhibition of the host defense mechanism rather than the disturbances of lipid metabolism.

4 악 상피세포는 계속해서 탈락하고 세포고사 (Apoptosis) 가 이 과정에 중요한 역 할윤 한다. 본 연구는 콘택프렌즈 착용으로 인한 각막의 부작용에 관여하는 Cytokine 증 어느 Cytokine 이 각막 상피세포의 세포고사를 유도하는지 조사하고자 시행하였다. 각딱 상피세포를 배양하여 4 종류의 인터루킨 OL-1a， IL-1,8, IL-6, IL-H) 과 인터 폐한 감마(l FNr) 그러고 종양괴사 인자 (TNFa‘ TNF，8)를 10 nM, 100 nM, 1μM 농도 포 2. 1, 7 일 동 안 처 리 하였 다. Hoechst :13342 형 광염 색 . Annexin V - FITC/Propi - dium Iodide( Pl) 염 색. TUNEL assay 그퍼 고 DNA Laddering을 시 행 하였 다. IL -la, IL .- 1,8. IL - G. IL - 8는 세 끊파사가 거 의 유도뇌 지 않았고 TNFa, TNF，8는 고농도에 서 약간의 세포고사룹 유도하였으며 IFNr에서는 10nM 에 4 일 동안 노출시 세포고사 가 유도되기 시작하였으며 농도와 노출기간에 비례하여 세포고사 빈도가 높아졌다. IFN -r는 콘택프렌즈로 인한 외상. 감염. 염증이 있을 때 방출되는데 각막상피 세포 고사와 각막병리에 관련이 있는 것으로 사료되며 각막상피세포의 항상성 유지에 중 요한 역할을 하는 것으로 생각된다.