니세틸 정(아세틸 - 엘 - 카르니틴 500mg)에 대한 뉴로세틸 정의 생물학적 동등성

조혜영,오인준,이용복,임동구,문재동,심영순,김은아,정현철 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.1

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, Nicetile^(TM) (Dong-A pharmaceutical Co., Ltd.) and Neurocetil^(TM) (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, 22.80±2.76 year in age and 63.07±7.98 ㎏ in body weight, were divided into two groups and a randomized 2 × 2 cross-over study was employed. After one tablet containing 500 ㎎ of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as AUC_t, C_(max) and T_(max) were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC_t, C_(max) and T_(max) between two tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the Nicetile^(TM) tablet. The powers (1-β) for AUC_t and C_(max) were 94.87% and 87.17%, respectively. Minimum detectable differences (△) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 15.58% and 19.16% AUC_t and C_(max), respectively). The 90% confidence intervals were within ±20% (e.g., -11.84∼6.41 and -10.57∼11.88 for AUC_t and C_(max), respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Neurocetil^(TM) tablet is bioequivalent to Nicetile^(TM) tablet.

A형 간염의 자연항체와 예방접종을 통한 항체 생성률의 역가 비교분석

권원현,김경화,조경아,문기춘,김정인,이인원,Kwon, Won Hyun,Kim, Kyung Hwa,Cho, Kyung A,Moon, Ki Choon,Kim, Jung In,Lee, In Won 대한핵의학기술학회 2013 핵의학 기술 Vol.17 No.2

2008년부터 A형 간염 환자들이 급속히 증가하고 본원에 내원하여 건진을 받는 대부분의 수검자들이 A형 간염(IgG) 항체 생성 유무에 관심이 많아지며 검사 건수가 증가하였다. 그에 따라 항체 검사결과가 cut-off값에 걸리는 검체가 많아져 원인을 분석하였더니 대부분 A형 간염 예방접종을 한 수검자들이었다. 이에 저자들은 건강증진센터에서 설문조사를 통하여 자연면역을 획득한 수검자들 그룹과 본원에서 A형 간염 예방접종(1차, 2차)을 실시한 직원들 그룹으로 나누어 검사를 시행하였고 cut-off값을 기준으로 항체 생성률과 그에 대한 역가를 비교하고 진단검사의학과와 핵의학과에서 사용하는 진단 시약간에 항체 생성률과 그에 대한 역가를 비교해 보고자 했고, 2012년 8월 한 달 동안 건진 수검자 185명을 설문조사하여 자연면역을 획득한 119명과 본원에서 예방 접종을 실시한 직원들을 대상으로 1차 접종자 53명, 2차 접종자 59명으로 대상을 분류했다. 항체 생성률은 cut-off값 1을 기준했을 때 0.90-1.10 (${\pm}$), 0.60-0.89 (1+), 0.30-0.59 (2+), 0.01-0.29 (3+)로 나누어 역가를 비교하고, 같은 기준으로 제조사별 백신 접종 후 항체 생성률에 대한 역가를 비교평가 해 보았다. 그 결과, 건진 수검자 중 자연 면역을 획득한 수검자는 cut-off값 1을 기준했을 때, 0.90-1.10 (${\pm}$)가 0%, 0.60-0.89 (1+)가 0%, 0.30-0.59 (2+)가 4.2%, 0.01-0.29 (3+)가 96%로 역가가 <0.60 ($${\geq_-}2+$$)가 100%였다. 그리고 예방접종을 실시한 직원들의 항체 생성률은 1차 접종자 중 ${\pm}$가 59.1%, 1+가 18.1%, 2+가 18.1%, 3+가 4.6%로 총 45.3%였고, 역가는 $${\geq_-}$$ 0.60 ($${\leq_-}1+$$)가 77.3%였다. 2차 접종자의 항체 생성률은 ${\pm}$가 1.9%, 1+가 15.4%, 2+가 36.54%, 3+가 46.2%로 총 88.1%였고 역가는 <0.60 ($${\geq_-}2+$$) 82.7%가 였다. 또한 제조사별로 비교 하였을 때 1차 접종자의 항체 생성률은 BNIBT 20.8% (${\pm}24.5%$), GB 15.7% (${\pm}7.8%$), RIAKEY 94.3% (${\pm}3.8%$), ROCHE 83% (${\pm}0%$), Abbot 73.1% (${\pm}5.8%$)였고, 2차 접종자의 항체 생성률은 BNIBT 86.4% (${\pm}1.7%$), GB 88.5% (${\pm}1.9%$), RIAKEY 100% (${\pm}0%$), ROCHE 98.3% (${\pm}0%$), Abbot 98.2% (${\pm}0%$)였다. 즉 자연면역 항체가 예방접종에 의한 항체보다 역가가 높다는 것을 알 수 있었고, 1차 접종 후 보다는 2차 접종 후 검사를 시행했을 때 항체 생성률과 역가가 대부분 높아짐을 알 수 있었다. 따라서 결과 보고시 negative, index (${\pm}$), weak positive (1+), positive (2+), strong positive (3+)로 역가를 나누어 보고를 하거나 결과값에 index값을 같이 적어서 결과를 상세히 보고한다면 과거결과와 비교도 가능할 것이다. 또 제조사별 비교 시 1차 예방접종 후의 항체 생성률과 역가에서 시약간에 많은 차이를 보이고 있었고, 매년 예방 접종률이 높아지고 있는 시점에서 이러한 차이를 줄이기 위해서 각 제조사들은 민감도나 재현성에 더 주의를 기울여야 하겠고, 자연면역항체와 예방접종을 통한 항체간에 생길 수 있는 미지의 차이를 감안하여 검사자들이 사용하는 시약을 신뢰할 수 있도록 더 연구하고 개발해야 할 것이다. Purpose: Since 2008, hepatitis A patients was rapidly increasing. So, Most of the health checkup examinees were interested in whether hepatitis A antibody was a lot. thereby The number of tests was increasing. In recent years, Antibody test results in the range of cut-off values were increased. According to the cause analysis, most examinees had a hepatitis A vaccine. This study was conducted to classify hepatitis A antibody as natural antibody and antibody after vaccination and compared the titer for seroconversion rate based on cut-off values. Materials and Methods: For a month in August 2012, First, We surveyed 185 health examinees and classified 119 health examinees who had acquired natural antibody. Second, for employees who were inoculated against hepatitis at our hospital, We classified into 53 primary inoculators and 59 secondary inculators. when the standard of cut-off value was 1, The seroconversion rate was compared the titer divided by 0.90-1.10 (${\pm}$), 0.60-0,89 (1+), 0.30-0.59 (2+), 0.01-0.29 (3+) and we compared the titer for seroconversion rate by each manufacturer after vaccination. Results: When the standard of cut-off value was 1, the titer of 119 health examinees who had acquired natural antibody was 0.90-1.10 (${\pm}$): 0%, 0.60-0.89 (1+): 0%, 0.30-0.59 (2+): 4.2%, 0.01-0.29 (3+): 96% and the titer of <0.60 ($${\geq_-}2+$$) was 100%. The titer of 53 primary inoculators was 0.90-1.10 (${\pm}:59.1%$), 0.60-0.89 (1+): 18.1%, 0.30-0.59 (2+): 18.1%, 0.01-0.29 (3+): 4.6% and the seroconversion rate was 45.3%. The titer of $${\geq_-}0.60$$ ($${\leq_-}1+$$) was 77.3%. The titer of 59 secondary inoculators was 0.90-1.10 (${\pm}:1.9%$), 0.60-0.89 (1+): 15.4%, 0.30-0.59 (2+): 36.54%, 0.01-0.29 (3+): 46.2% and the seroconversion rate was 88.1%. The titer of <0.60 ($${\geq_-}2+$$) was 82.7%. When we compared the titer for seroconversion rate by each manufacturer after vaccination, the seroconversion rate of 53 primary inoculators was BNIBT: 20.8% (${\pm}:24.5%$), GB: 15.7% (${\pm}:7.8%$), RIAKEY: 94.3% (${\pm}:3.8%$), ROCHE: 83% (${\pm}:0%$), ABBOTT: 73.1% (${\pm}:5.8%$) and the seroconversion rate of 59 secondary inoculators was BNIBT : 86.4% (${\pm}:1.7%$), GB: 88.5% (${\pm}:1.9%$), RIAKEY: 100% (${\pm}:0%$), ROCHE: 98.3% (${\pm}:0%$), ABBOTT: 98.2% (${\pm}:0%$). Conclusion: The study show that the titer of natural immune antibodies is higher than the titer of vaccination and the titer of secondary inoculation is mainly higher than the titer of primary inoculation. Consequently, if we know the titer of hepatitis A antibodies, it will help to give resullt reports. And then, when we compared the titer and the seroconversion rate by each manufacturer, There was a very distinct difference. As the test subjects inoculate against hepatitis A (HAV), it is considered BNIBT, GB will occur false negative rate and RIAKEY, ROCHE, ABOTT will occur false positive rate.

Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Selective A_(3) Adenosine Receptor Agonists

Hwang, Ki-Jun,Chun, Moon-Woo,Jacobson, Kenneth A.,Jeong, Lak-Shin,Lee, Jeong-A,Moon, Hyung-Ryong,Kim, Hea-Ok,Kim, Kyung-Ran,Lee, Kang-Man,Kim, Bum-Tae 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.16

On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a- d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating· lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-4, 6, and 7 did not show significant inhibitory activity against S-adenosylllolllocysteine hydrolase (SAH) up to 100 ㎛, maybe due to the absence of the secondary hydroxyl group at tile C3'-position, which should be oxidized by cofactor-bound NAD^(+). However, aplo-neplanocin A (5a) showed potent and highly selective binding affinity (K_(i), = 628 ± 69 nM) at the A_(3) adenosine receptor without any binding affinity at the A_(1) and A_(2A) adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugarsusing stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A_(3) adenosine receptor agonist, which play a great rote in developing new A_(3) adenosine receptor agonist as well as in identifying the binding site of the receptor.

Description of Helicotylenchus zeidani sp. nov., a new species of nematode from Guneid sugarcane, Sudan

G.A.A. Elbadri,Il Sung Moon,P. Wani,K. Bukhari,이동운,추호렬 한국응용곤충학회 2009 Journal of Asia-Pacific Entomology Vol.12 No.3

A study was done on the taxonomy and morphology of plant parasitic nematodes (Tylenchida) found in a Guneid sugarcane factory field of Saccharum officinarum (sugarcane), in Gezira state, Sudan. The sampleswere collected from around the root zone of sugarcane stools at a depth of 10 to 15 cm. One new species belonging to Hoplolaimidae was identified and studied. Helicotylenchus zeidani sp. nov. is characterized by a smooth head and a conical tail with a projection. It is 0.72 mm (0.62 to 0.81 mm) long, a=32.4 (25.6 to 36.6), c=36.9 (29.2 to 53.1) with a medium sized body and shorter stylet.

Gynecologic manifestation and identification of genetic causes of Klippel-Trenaunay syndrome

( A Mi Roh ),( Sa Ra Lee ),( Young Mee Lim ),( Kyung Ah Jeong ),( Hye Sung Moon ),( Hyewon Chung ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by malformations of the arteries, capillaries, veins and lymphatic system, surrounding soft tissue and bone hypertrophy. A. Timur et al. (2005) and others have reported that AGGF1 gene causes excessive angiogenesis in KTS. In addition, Fabio C. Vicentini (2006) and others introduced cases involving bladder and vulva. However, there has been no genetic study of KTS patients who have invaded the clitoris. In this study, whole genome sequencing of KTS patients and their families involving vulva were performed to identify KTS - related genes and to confirm genetic variants in KTS. A 26 year old woman visited OBGY clinic for protruding vaginal mass. On examination, the purplish protruding anterior vaginal wall was noted and a 1.5 x 1.5 cm sized clitoral mass was also noted. A sessile type elevated skin lesion causing itching and irritation symptom was noted on both buttock. She had suffered heavy menstrual bleeding and on pelvic MRI, a upward displacement of uterus was noted near umbilicus level. NSAIDs prescribed onthe first 3 days of menstruation decreased the menstrual blood loss upto 40percent. In this study, whole genome sequencing of a KTS patient involving vulva was performed to identify KTS - related genes and to confirm genetic variation. The patient's peripheral blood and a sessile mass around buttock was sampled and whole genome sequencing was performed. Most KTS has known to be a sporadic one, however some genetic variants has been reported.

동해 남부 연안 해역에서 냉수대 발생이 식물플랑크톤 군집에 미치는 영향

김아람,윤석현,정미희,윤상철,문창호,Kim, A-Ram,Youn, Seok-Hyun,Chung, Mi-Hee,Yoon, Sang-Chol,Moon, Chang-Ho 한국해양학회 2014 바다 Vol.19 No.4

냉수대 발생 전 후의 해양 환경과 식물플랑크톤 군집 구조 및 크기를 파악을 위해 여름철 빈번하게 냉수대가 발생되는 동해 남부 해역(울산 정자~부산 일광) 18개 정점에서 2013년 5월부터 8월까지 냉수대 발생 환경 및 식물플랑크톤 군집 구조를 조사하였다. 냉수대는 7월과 8월에 연안 정점(A1, B1, C1)에서 발생하였고, 표층에서 저온 고염의 특성을 보였다. 이 시기에 영양염은 수온과 유의한 음의 상관관계(DIP, r=-0.218, p<0.01; DIN, r=-0.306, p<0.01; silicate, r=-0.274, p<0.01)를 보여, 찬 해수가 분포하는 표층에 영양염이 풍부함을 알 수 있었다. 출현한 식물플랑크톤은 총 186종이었고, 현존량은 5월(C1, $726{\times}10^3cells\;L^{-1}$)과 7월(A1, $539{\times}10^3cells\;L^{-1}$)에 높았다. 또한, 연안 정점에서 총 chl. a 와 소형플랑크톤 chl. a ($>20{\mu}m$)의 농도가 냉수대 발생 시기인 7, 8월에 뚜렷하게 증가한 반면, 수온약층이 형성된 6월에는 현저하게 낮았다. 6월의 우점종은 Pseudo-nitzschia spp.이었고, 그 세포 크기는 $309{\mu}m^3$로 다른 시기의 식물플랑크톤의 1/10 수준에 머무는 작은 크기였다. 이러한 결과는 7월과 8월에 총 chl. a의 증가와 식물플랑크톤의 크기 증가가 냉수대 발생 시에 표층으로 공급된 영양염의 영향임을 시사한다. 이러한 해양 환경 특성과 식물플랑크톤 출현양상은 연안 정점에서 뚜렷하게 보였고, 외측 정점에서는 관찰되지 않았다. 이 연구에서는 동해 남부 해역에서 냉수대가 발생하면 식물플랑크톤의 현존량 증가와 더불어 비교적 크기가 큰 식물플랑크톤의 출현 빈도가 증가하는 현상을 확인하였다. 결과적으로 하계에도 불구하고 동해 남부 연안 해역에서 냉수대 발생에 따른 영양염 공급은 식물플랑크톤 군집조성과 현존량에 상당한 영향을 미치는 것으로 판단된다. In order to understand environment condition and phytoplankton community before and after coastal upwelling, the influences of upwelling events on phytoplankton community were studied at 18 stations located the Southern part of East Sea, Korea from May to August 2013. The surface water masses showed low temperature and high salinity due to upwelling events at coastal stations (A1, B1, C1). Correlation between temperature and nutrients (DIP, r=-0.218, p<0.01; DIN, r=-0.306, p<0.01; silicate, r=-0.274, p<0.01) was significantly negative. This result could be explained that nutrients were supplied to surface water by the upwelling of bottom water. Phytoplankton communities were composed of 186 species. Phytoplankton abundance were relatively high in May (C1, $726{\times}10^3cells\;L^{-1}$) and July (A1, $539{\times}10^3cells\;L^{-1}$). Total chlorophyll a and micro-size fraction ($>20{\mu}m$) increased at coastal stations in July and August, while phytoplankton abundance and total chl. a was much low in June. Dominant species in June was Pseudo-nitzschia spp. of which the cell size was $309{\mu}m^3$. Cell size of Pseudo-nitzschia spp. was smaller than dominant species in other period. Therefore, the increase in total chloro-phyll a and the size of phytoplankton was resulted in the sufficient supply of nutrients. In contrast, these tendencies were not observed at outside stations. These results suggested that coastal upwelling was an important influencing factor to determine the species composition and standing stock of phytoplankton community in the coastal waters of the Southern part of East Sea, Korea.

UPLC-PDA를 이용한 창포류의 분류 및 함량 분석

조지은(Ji Eun Jo),이아영(A Yeong Lee),김효선(Hyo Seon Kim),문병철(Byeong Cheol Moon),지윤의(Yunui Ji),천진미(Jin Mi Chun),김호경(Ho Kyoung Kim) 한국식품과학회 2013 한국식품과학회지 Vol.45 No.3

A quantitative method using ultra performance liquid chromatography with a photodiode array detector (UPLCPDA) was established for the analysis of 2 major plant metabolites: β-asarone and α-asarone from Acorus gramineus, A. tatarinowii, A. calamus and Anemone altaica, and their contents are compared with other herbs of Acorus species. The method was validated according to the International Conference on harmonization (ICH) guideline for validation of analytical procedures with respect to precision, accuracy, and linearity. The average content of β-asarone in Acorus gramineus was significantly higher than that in others, with the second highest concentration observed in A. tatarinowii, and only a trace amounts found in A. calamus and Anemone altaica. In contrast, the average content of α-asarone in A. calamus was the highest, followed by that in Acorus gramineus and A. tatarinowii. principle component analysis (PCA) confirmed that β-asarone and α-asarone content differed among the species. These results suggest that this UPLC-PDA method can be considered as good quality control criteria for Acorus gramineus.

IN-1130, a novel transforming growth factor-β type I receptor kinase (ALK5) inhibitor, suppresses renal fibrosis in obstructive nephropathy

Moon, J-A,Kim, H-T,Cho, I-S,Sheen, YY,Kim, D-K 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.17

The transforming growth factor-β(TGF-β) plays a central role in the progression of renal fibrosis. TGF-β transduces its signal through the activin receptor-like kinase (ALK)5. IN-1130, a novel small molecule ALK5 inhibitor, inhibited the purified kinase domain of ALKS-mediated Smad3 phosphorylation with an IC_(50) value of 5.3 nM. IN-1130 proved to be highly selective in a panel of 27 serine/threonine and tyrosine kinases including p38α mitogen-activated protein kinase. We evaluated the efficacy of IN-1130 to block renal fibrogenesis induced by unilateral ureteral obstruction (UUO) in rats. Either vehicle (saline) or IN-1130 (10 and 20mg/kg/ day) was intraperitoneally administered to UUO rats for 7 and 14 days. Phosphorylated Smad2 (PSmad2) and markers of fibrosis were analyzed in kidney tissues, In UUO control kidneys, interstitial fibrosis including tubular atrophy, loss and dilation, inflammatory cell infiltration, and fibroblast cell proliferation was prominent. These morphological changes were notably reduced by 1N-1130 treatment. IN-1130 decreased levels of TGF-/β1 messenger RNA (mRNA), type I collagen mRNA, and pSmad2, compared to UUO control rats. As determined by measuring the hydroxyproline content, total kidney collagen amount was increased in UUO control kidneys, but significantly reduced by IN-1130 treatment, which was comparable to results of histochemical staining for collagen. IN-1130 also suppressed the expression of a-smooth muscle actin (a-SMA) and fibronectin in UUO kidneys. Our results show that IN-1130 suppressed the fibrogenic process of UUO, further underscoring the potential clinical benefits of IN-1130 in the treatment of renal fibrosis.

Discovery of a New Nucleoside Template for Human A₃ Adenosine Receptor Ligands : D-4'-Thioadenosine Derivatives without 4'-Hydroxymethyl Group as Highly Potent and Selective Antagonists

Jeong, Lak Shin,Choe, Seung Ah,Gunaga, Prashantha,Kim, Hea Ok,Lee, Hyuk Woo,Lee, Sang Kook,Tosh, Dilip K.,Patel, Amit,Palaniappan, Krishnan K.,Gao, Zhan-Guo,Jacobson, Kenneth A.,Moon, Hyung Ryong 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.18

Truncated D-4'-thioadenosine derivatives lacking the 4'-hydroxymethylene moiety were synthesized starting from D-mannose, using cyclization to the 4-thiosugar and one-step conversion of the diol to the acetate as key steps At the human A₃ adenosine receptor (AR), N^(6)-substituted purine analogues bound potently and selectively and acted as antagonists in a cyclic AMP functional assay An N^(6)-(3-chlorobenzyl)purine analogue 9b displayed a K, value of 1 66 nM at the human A₃ AR Thus, truncated D-4'-thioadenosine is an excellent template for Ihe design of novel A₃ AR antagonists to act at both human and murine species.

Matrix Metalloproteinase-8 Plays a Pivotal Role in Neuroinflammation by Modulating TNF-α Activation

Lee, Eun-Jung,Han, Jeong Eun,Woo, Moon-Sook,Shin, Jin A.,Park, Eun-Mi,Kang, Jihee Lee,Moon, Pyong Gon,Baek, Moon-Chang,Son, Woo-Sung,Ko, Young Tag,Choi, Ji Woong,Kim, Hee-Sun The American Association of Immunologists, Inc. 2014 JOURNAL OF IMMUNOLOGY Vol.193 No.5

<P>Matrix metalloproteinases (MMPs) play important roles in normal brain development and synaptic plasticity, although aberrant expression of MMPs leads to brain damage, including blood–brain barrier disruption, inflammation, demyelination, and neuronal cell death. In this article, we report that MMP-8 is upregulated in LPS-stimulated BV2 microglial cells and primary cultured microglia, and treatment of MMP-8 inhibitor (M8I) or MMP-8 short hairpin RNA suppresses proinflammatory molecules, particularly TNF-α secretion. Subsequent experiments showed that MMP-8 exhibits TNF-α–converting enzyme (TACE) activity by cleaving the prodomain of TNF-α (A<SUP>74</SUP>/Q<SUP>75</SUP>, A<SUP>76</SUP>/V<SUP>77</SUP> residues) and, furthermore, that M8I inhibits TACE activity more efficiently than TAPI-0, a general TACE inhibitor. Biochemical analysis of the underlying anti-inflammatory mechanisms of M8I revealed that it inhibits MAPK phosphorylation, NF-κB/AP-1 activity, and reactive oxygen species production. Further support for the proinflammatory role of microglial MMP-8 was obtained from an in vivo animal model of neuroinflammatory disorder. MMP-8 is upregulated in septic conditions, particularly in microglia. Administration of M8I or MMP-8 short hairpin RNA significantly inhibits microglial activation and expression/secretion of TNF-α in brain tissue, serum, and cerebrospinal fluid of LPS-induced septic mice. These results demonstrate that MMP-8 critically mediates microglial activation by modulating TNF-α activity, which may explain neuroinflammation in septic mouse brain.</P>