The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 489
Slide Session
K-LG-11 Lower GI Tract
Guggulsterone Ameliorates Colitis by Blocking Crosstalk Between Nf- κb and Trem-1
Soo Jung Park1, Ki Cheong Park1, You Hyun Kang1, Hyun A Jin1, Xiumei Che1, Seung Won Kim1, Sung Pil Hong1, Tae Il Kim1, Won Ho Kim1, Jae Hee Cheon1
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Korea1
Background: Triggering receptor expressed on myeloid cells (TREM)-1 constitutively expressed in macrophage, and upregulated by bacterial components, such as lipopoly- saccharide (LPS), and functions as an amplifying molecule in infl ammatory responses.
Recent studies have reported that TREM-1 expression is up-regulated in patients with infl ammatory bowel disease (IBD). In this study, we expected that guggulsterone (GGS) functions as reducer of TREM-1 in macrophage and investigated the anti-infl amma- tory effects of GGS via the inhibition of NF-κB/TREM-1 in mononuclear cells using RAW264.7 activated by LPS and TNBS-induced colitis model of knockout mice.
Methods: We are checked the mRNA level of TREM-1 and toll like receptor 4 (TLR4) using real time RT-PCR and the protein level of IκBa and phospho-IκBa using west- ern blotting and ELISA, and nuclear translocation of NF-κB using immunofl uores- cence. MG132 and TREM-1 antibody were used to determine the interaction of NF-κ B and TREM-1 signaling. Mouse colitis is induced by the administration of TNBS into the colon.
Results: GGS treatment decreased the mRNA and protein levels of TREM-1, TLR4, TNF-a, IL-6, IL17, COX-2, and MMP-9 by blocking the phosphorylation and degrada- tion of IκBa as well as nuclear translocation of NF-κB in RAW264.7 macrophage ac- tivated by LPS. In the TNBS-induced colitis model, GGS reduced disease activity index (DAI), and infl ammation related protein expressions by suppressing NF-κB and TREM- 1 activation in colon mucosa.
Conclusions: GGS blocks the NF-κB signaling pathway by targeting the TREM-1 in RAW264.7 macrophage activated by LPS and TNBS-induced mouse colitis model. Our results provide an insight into the mutual relationship NF-κB and TREM-1 signaling pathway. Eventually, these fi ndings shows that GGS has a anti-infl ammatory effects in macrophage cells through the regulation of the TREM-1 and NF-κB signaling, which suggests that GGS is a potential therapeutic agent for the treatment of IBD.
K-LG-12 Lower GI Tract
Nimbolide Inhibits Nuclear Factor- κb Signaling in Peritoneal Macrophages and Ameliorates Experimental Colitis in Mice
Ji Yeon Seo1, Jaeyoung Chun1, Changhyun Lee2, Sung Wook Hwang1, Jong Pil Im1, Joo Sung Kim1
Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medi- cine, Korea1, Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Korea2
Background: Nimbolide is a limonoids extracted from neem tree (Azadirachta indica) which shows the anti-infl ammatory effect. We investigated the effect of nimbolide on nuclear factor-kappa B (NF-κB) signaling pathway in peritoneal macrophages and on experimental murine colitis model.
Methods: Peritoneal macrophages were treated with or without nimbolide and stim- ulated with tumor necrosis factor-a (TNF-a). Protein expression of interleukin (IL)-6, IL-8, and IL-12 were examined by ELISA. The effect of nimbolide on NF-κB pathway was examined by Western blot analysis of IKBa phosphorylation/degradation. Electro- phoretic mobility shift assay was also performed to verify the DNA binding activity of NF-κB. For in vivo study, dextran sulfate sodium (DSS)-induced acute colitis model in C57BL/6 wild-type mice was used. Colitis was quantifi ed by disease activity index, colon length and histopathologic evaluation.
Results: Nimbolide inhibited the expression of pro-infl ammatory cytokines such as IL-6, IL-8 and IL-12 in peritoneal macrophages. It also inhibited IκBa phosphoryl- ation/degradation and DNA binding activity of NF-κB in macrophage signifi cantly.
Nimbolide was effective in DSS-induced acute colitis model. It improved weight loss, shortening of colon length, disease activity index and histologic score signifi cantly compared to control.
Conclusions: Nimbolide inhibits NF-κB signaling by suppressing IKBa phosphorylation and nuclear binding of NF-κB in macrophages and ameliorates experimental colitis.
This suggests that nimbolide could be a potential therapeutic agent for infl ammatory bowel disease.
K-LG-13 Lower GI Tract
Clinical Features and Prognosis of Fistulizing Perianal Crohn’s Disease in Korea: Results from the Connect Study
Jaeyoung Chun1, Sung Wook Hwang1, Jee Hyun Kim1, Jong Pil Im1, Jae Hee Cheon2, Byong Duk Ye3, Ji Won Kim4, You Sun Kim5, Joo Sung Kim1
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea1, Department of Internal Medicine, Yonsei University College of Medicine, Korea2, Department of Internal Medicine, University of Ulsan College of Medicine, Korea3, Department of Internal Medicine, Seoul National University Boramae Hospital, Korea4, Department of Internal Medicine, Inje University College of Medicine, Korea5
Background: The disease course and poor prognostic factors in Korean patients with Crohn’s disease (CD) has not been fully determined. The aim of this study is to assess the clinical characteristics and long-term outcomes of CD patients according to the presence of perianal fi stula.
Methods: This retrospective cohort study enrolled patients diagnosed with CD between July 1982 and December 2008 from 29 hospitals in Korea. Those who had a follow-up shorter than 12 months were excluded. The primary endpoints were CD-related complications including non-perianal fi stula, stricture, and in- tra-abdominal abscess.
Results: A total of 1,193 CD patients were enrolled. Mean follow-up period was 8.46 years (range, 1.0-26.4). Four hundred sixty-five (39.0%) CD patients experienced perianal fi stula. Fistulizing perianal CD was signifi cantly associated with younger age (<40 years old), male gender, diagnosis of CD at primary or secondary care clinics, and ileocolonic involvement. Complications of non-peri- anal fi stula (p=0.025) and intra-abdominal abscess (p=0.003) were signifi cantly more common in patients with fistulizing perianal CD than in those without fi stulizing perianal CD. In contrast, complicated stricture was not associated with perianal fi stula. Independent risk factors for non-perianal fi stula were perianal fi stula (adjusted hazard ratio [HR], 1.47; 95% confi dence interval [CI], 1.09-1.99;
p=0.011), female (adjusted HR, 1.46; 95% CI, 1.08-1.98; p=0.014), diagnosis of CD at referral hospital (adjusted HR, 1.72; 95% CI, 1.13-2.62; p=0.011), and up- per gastrointestinal involvement (adjusted HR, 1.87; 95% CI, 1.37-2.55; p<0.001).
Furthermore, perianal fistula (adjusted HR, 1.37; 95% CI, 1.01-1.88; p=0.046) and upper gastrointestinal involvement (adjusted HR, 1.48; 95% CI, 1.05-2.07;
p=0.025) signifi cantly increased the risk of intra-abdominal abscess.
Conclusions: Perianal fi stula predicts development of non-perianal fi stula and in- tra-abdominal abscess in CD patients. Therefore, patients with fi stulizing perianal CD should be carefully monitored for the complicated fi stula.
