Interleukin 17 (IL-17) Increases the Expression of Toll-like Receptor-2, 4, and 9 by Increasing IL-1β and IL-6 Production in Autoimmune Arthritis

LEE, JUN-HEE,CHO, MI-LA,KIM, JU-IN,MOON, YOUNG-MEE,OH, HYE-JWA,KIM, GEUN-TAE,RYU, SUN,BAEK, SEUNG-HOON,LEE, SUN-HEE,KIM, HO-YOUN,KIM, SUNG-IL The Journal of Rheumatology 2009 The Journal of rheumatology Vol.36 No.4

<B>Objective.</B><P>To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.</P><B>Methods.</B><P>On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR.</P><B>Results.</B><P>In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6.</P><B>Conclusion.</B><P>IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.</P>

류마티스 관절염 동물 모델에서 활막의 RANKL/OPG mRNA 발현 비율 및 IL-17의 효과

이준희 ( Jun Hee Lee ),김근태 ( Geun Tae Kim ),류선 ( Sun Ryu ),김주인 ( Ju In Kim ),백승훈 ( Seung Hoon Baek ),김성일 ( Sung Il Kim ) 대한류마티스학회 2006 대한류마티스학회지 Vol.13 No.2

Objective: To investigate the synovial mRNA expression of receptor activator of NFκB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG mRNA expression ratio, and to evaluate the effects of IL-17 in experimental rheumatoid arthritis (RA) model. Methods: After induction of collagen-induced arthritis (CIA) by type II collagen in DBA1 mice, mice were anesthetized at day 28 and a small aperture in the skin of the knee was performed. Mice, in which arthritis of knee was present, were selected and divided into 3 groups, and phosphate-buffered saline (PBS group), IL-17 (IL-17 group) or anti-IL-17 monoclonal antibody (anti-IL-17 group) was injected to both knee joint at day 28 and 32. At day 35, mice were sacrificed and synovium of knee joints were isolated. Synovial mRNA expression of RANKL, RANK and OPG was assessed by real-time RT-PCR and immunohistochemical stain. Results: Synovial RANKL and RANK mRNA expressions were significantly different among IL-17, PBS, anti-IL-17 and normal group (IL-17>PBS>anti-IL-17>normal group), and synovial OPG mRNA expressions in PBS, IL-17 and anti-IL-17 group were significantly high than those in normal group, however, there was no significant difference among IL-17, PBS and anti-IL-17 group. RANKL/OPG mRNA ratio was significantly different among these groups (IL-17>PBS>anti-IL-17>normal group). In immunohistochemical stain, RANKL, RANK and OPG-positive cells were expressed at synovium. Conclusion: Synovial RANKL/OPG mRNA ratio was enhanced in CIA, and IL-17 induced higher RANKL/OPG ratio in the synovium of CIA, which was blocked by anti-IL-17 antibody. These results suggest that RANKL/OPG mRNA ratio play an important roles on bone destruction, and IL-17 may be actively involved in bone destruction by enhancing RANKL/OPG ratio in CIA model.

류마티스 관절염 동물 모델에서 Toll-Like Receptors의 발현

이준희 ( Jun Hee Lee ),이수봉 ( Soo Bong Lee ),김근태 ( Geun Tae Kim ),류선 ( Sun Ryu ),김주인 ( Ju In Kim ),이선희 ( Sun Hee Lee ),김성일 ( Sung Il Kim ) 대한류마티스학회 2006 대한류마티스학회지 Vol.13 No.2

Objective: To evaluate the expression of Toll-like receptor (TLR) 2, 4 and 9 and investigate the effects of IL-17 on the expression of TLRs in experimental rheumatoid arthritis (RA) model. Methods: After induction of collagen-induced arthritis (CIA) by type II collagen in DBA1 mice, phosphate-buffered saline (PBS, PBS group) or IL-17 (IL-17 group) was injected to both knee joint at day 28 and 32. At day 35, mice were sacrificed and knee joints were isolated. Synovial mRNA expressions of TLR-2, 4 and 9 determined by real-time RT-PCR were compared among normal DBA1 mice (normal group), PBS and IL-17 group. Results: Synovial TLR-2, 4, and 9 mRNA expressions of IL-17 and PBS group were significantly higher than normal group, and those of IL-17 group were higher than PBS group. Conclusion: Synovial TLR-2, 4 and 9 expression was enhanced in CIA and up-regulated by local overexpression of IL-17. These results suggest that TLRs play a roles on CIA and IL-17 induced aggravation of arthritis in CIA.

Chronic alcohol consumption induces migration of IL-1R2+ monocytes from the bone marrow into the liver by neuro-immunologic pathway

Young-Ri Shim,Hee-Hoon Kim,Keungmo Yang,Tom Ryu,Kyurae Kim,Sung Eun Choi,Minjeong Kim,Chae-Rin Woo,Young-Sun Lee,Won-Il Jeong 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Liver is challenged by diverse detrimental substances through multiple metabolic processes, but it is less prone to inflammation. In chronic alcohol consumption, although the migration of monocytes from bone marrow (BM) into liver is increased, alcoholic hepatitis rarely occurs. Thus, we investigated the sub-population of liver macrophages showing anti-inflammatory roles through single-cell RNA sequencing (scRNA-Seq) after chronic EtOH-feeding. Interestingly, in scRNA-seq and flow cytometry analyses of hepatic macrophages, the phenotype of Ly6Clow (anti-inflammatory) cells was dramatically altered by ethanol intake. In particular, they were highly expressed interleukin-1 type II receptor (IL-1R2), a decoy receptor of IL-1β. Intriguingly, IL-1R2+ Ly6Clow macrophages showed decreased CX3CR1 expression, which was confirmed not only in the liver, but also BM and blood, suggesting monocytes from BM affected by ethanol might migrate into the liver. We found that the Leptin Receptor+ mesenchymal stromal cells (LepR+ MSCs), which were located around blood vessels expressing CX3CL1 to hold CX3CR1+ macrophages, could express alcohol dehydrogenase to metabolize ethanol in BM. Ethanol metabolism in LepR+ MSCs was induced both production of chemokines (CXCL9 and 10) and the excretion of glutamate via cystine-glutamate anti-porter xCT to recruit and activate the CXCR3+ BM NK cells to produce interferon-γ in a metabotropic glutamate receptor 5 (mGluR5)-dependent manner. Indeed, IFN-γ production was significantly decreased in EtOH-fed mice when we depleted mGluR5 in NK cells. In turn, NK cell-derived IFN-γ down-regulated CX3CR1 expression in BM Ly6Clow monocytes, consequently induced egress of Ly6Clow monocytes into the blood and migration into the liver to suppress alcoholic inflammation. In conclusion, glutamate of LepR+ MSCs imposed egress license on anti-inflammatory IL-1R2+ Ly6Clow monocytes through NK cell-derived IFN-γ-mediated suppression of CX3CR1, suggesting a potential therapeutic inter-organ crosstalk between BM and liver in alcoholic liver disease.

Interleukin-17이 배양된 류마티스 관절염 활막세포에서 Matrix Metalloproteinase-3의 생성에 미치는 영향

류선 ( Sun Ryu ),김성일 ( Sung Il Kim ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.1

Objective: To investigate the effect of interleukin-17 (IL-17) on the production of matrix metalloproteinase-3 (MMP-3) and the expression of MMP-3 mRNA in rheumatoid arthritis synoviocytes. Methods: Fibroblast-like synovial cells (FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of various concentration of IL-17. The production of MMP-3 and expression of MMP-3 mRNA were determined by sandwitch ELISA and real-time quantitative RT-PCR. Results: In ELISA, stimulation of FLS by IL-17 with 5, 10, 20, 40 ng/mL concentrations increased the production of MMP-3 by 2.7, 2.9, 3.1, 3.6 fold after 24 hours and 9.9, 10, 11, 12 fold after 48 hours over the constitutive levels of unstimulated FLS. In real-time quantitative RT-PCR, stimulation of FLS by IL-17 with 5, 10, 20, 40 ng/mL concentrations increased the MMP-3/β-actin mRNA ratio by 3.2, 5.7, 9.9, 30.5 fold after 24 hours over the constitutive levels of unstimulated FLS.

Anti-inflammatory effect of polyphenol-rich extract from the red alga Callophyllis japonica in lipopolysaccharide-induced RAW 264.7 macrophages

Ryu, BoMi,Choi, Il-Whan,Qian, Zhong-Ji,Heo, Soo-Jin,Kang, Do-Hyung,Oh, Chulhong,Jeon, You-Jin,Jang, Chul Ho,Park, Won Sun,Kang, Kyong-Hwa,Je, Jae-Young,Kim, Se-Kwon,Kim, Young-Mog,Ko, Seok-Chun,Kim, G The Korean Society of Phycology 2014 ALGAE Vol.29 No.4

Despite the extensive literature on marine algae over the past few decades, a paucity of published research and studies exists on red algae. The purpose of this study was to evaluate the potential therapeutic properties of the ethanol extract of the red alga Callophyllis japonica against lipopolysaccharide (LPS)-stimulated macrophage inflammation. The C. japonica extract (CJE) significantly inhibited the nitric oxide (NO) production and the induced dose-dependent reduction of the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, the CJE reduced the mRNA levels of inflammatory cytokines, including tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6. We investigated the mechanism by which the CJE inhibits NO by examining the level of mitogen-activated protein kinases (MAPKs) activation, which is an inflammation-induced signaling pathway in macrophages. The CJE significantly suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38 MAPK. Taken together, the results of this study demonstrate that the CJE inhibits LPS-induced inflammation by blocking the MAPK pathway in macrophages.

하고초(夏枯草)가 흰쥐의 관절강내 Collagenase 투여로 인한 관절연골의 Proteoglycan 변성에 미치는 영향

류헌식 ( Heon Sik Ryu ),정수현 ( Su Hyeon Jeong ),김순중 ( Sun Jung Kim ),서일복 ( Il Bok Seo ) 한방재활의학과학회 2007 한방재활의학과학회지 Vol.17 No.1

Objectives: This study was to investigate the effects of Prunellae Herba on Proteoglycan(PG) degradation by measuring body weight, Glycosaminoglycan(GAG), Interleukin-1β(IL-1β) in synovial fluid, and PG content of articular cartilage of femur in collagenase-induced arthritis in rats. Methods :Arthritis was induced by injection of collagenase(0.1 ml) into knee joint of rats. Arthritic rats were divided into control(n=8) and treated( n=8) group. Control group was taken normal saline for 15 days and treated group was taken extracts of Prunellae Herba for same duration. Normal group(n=8), non-arthritic group, was injected with normal saline and was taken normal saline for 15 days. Body weight was measured at 0, 10, 15 days after injection. GAG, IL-1β in synovial fluid were measured with ELISA kit at 15 days after injection. PG content of articular cartilage of femur, represented by safranine O staining, was measured at 15 days after injection. Histopathological study on the articular cartilage of knee joint was investigated at 15 days after injection. Results : Body weight of treated group was not significantly increased, PG of treated group was significantly increased, and GAG was significantly decreased compared with control group. But IL-1β was not significantly decreased. Conclusions : On the basis of these results, we concluded that Prunellae Herba has inhibiting effects on the Proteoglycan degradation in collagenase-induced rat osteoarthritis model

過敏性쇼크가 組織肥滿細胞에 미치는 영향

劉基善,劉一晟,崔月鳳 최신의학사 1968 最新醫學 Vol.11 No.10

The authors present here the following results showing the effect of horse serum to mast cells in mesentery and gasto-intestinal tract, using adult male mice (D.D.O./Lee System) weighing under 20 gm seized with antibody-formation and anaphylactic shock by a normal horse serum injection. 1. In normal group the must cells counted comparatively 32.6 in mesentery, 64.6 in gastrointestinal tract,. the majority of which -was of deep-stained polygranules. 2. In sensitized group the mast cells counted without significant distinction of number as compared with normal group while 4 slight a-granulocytosis and reduced stain-ability were found. 3. In anaphylactic shock group reduction of granules as well as mast cells in number, vacuolation and extra-cellular phenomenon were remarkably found.

마늘, 고추 및 커피經口投與가 흰쥐 胃腸管 Enterochromaffin Cell에 미치는 영향

劉基善,劉一晟 최신의학사 1968 最新醫學 Vol.11 No.10

The authors present here the following results showing the effect of a tolerable quantity of garlic, cayenne and coffee to the enterod romafTin cells in the gastro-intestinal mucosa of albino rats weighing under 200 g, as well as the histological figure on the above mentioned mucosa. 1. A slight epithelial desquamation and tissue edema were found in the gastric body and pyloric portion of, albino rats. .2. The enterochromaffin cells decreased remarkably in number in cayenne-tested group and tended also to decrease in general in garlic or coffee-tested groups of albino rats

TV 속에 나타난 식생활관련 정보의 모니터 사례 분석

류혜숙,김현숙,양일선,김기태,배미용 대한영양사협회 2003 대한영양사협회 학술지 Vol.9 No.2

The purpose of this study was to analyze information about food and nutrition topics presented throughout the television broadcast media, thereby suggest the optimal communication method to give right information to the general public. To perform this study, total sixteen monitoring people were recruited and trained through monitoring practice before and during the study. Five domestic TV channels were selected to be monitored, for six months. For the best efficiency, all the monitoring people were divided into 8 teams based on the regional consideration. The statistical analysis of data was completed using SAS program. The main results of this study are as follows. First, the total reporting cases of information about foods and nutrition were 237, among which about 30% was classified as appropriate and 70% as inappropriate based on the trained monitors' evaluation. Second, the analysis of contents about incorrect informations showed that the insufficient descriptions of terminology and contents were the highest. And insufficient scientific evidences, incorrect contents excessively entertainment-oriented, no provision of alternatives, improper selection of expert advisors were followed. These results suggest that systematical monitoring should be continued to reduce the frequency of incorrect communication thereby give the right information in food and nutrition area to the general public. And there should be a closely cooperated system to provide the professional information to broadcasting production team by establishing the strategic program. In order to do that, most importantly the advisory team should be organized to professionally connect mass media to corresponding specialists. In addition, more educational programs about food and nutrition should be developed provide right information to the general public.