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REVIEW : Antimicrobial Proteins in Intestine and Inflammatory Bowel Diseases
( Jung Mogg Kim ) 대한장연구학회 2014 Intestinal Research Vol.12 No.1
Mucosal surface of the intestinal tract is continuously exposed to a large number of microorganisms. To manage the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins (AMPs) that directly kill or inhibit the growth of microorganisms. Thus, AMPs are important components of innate immunity in the gut mucosa. They are frequently expressed in response to colonic inflammation and infection. Expression of many AMPs, including human β-defensin 2-4 and cathelicidin, is induced in response to invasion of pathogens or enteric microbiota into the mucosal barrier. In contrast, some AMPs, including human α-defensin 5-6 and human β-defensin 1, are constitutively expressed without microbial contact or invasion. In addition, specific AMPs are reported to be associated with inflammatory bowel disease (IBD) due to altered expression of AMPs or development of autoantibodies against AMPs. The advanced knowledge for AMPs expression in IBD can lead to its potential use as biomarkers for disease activity. Although the administration of exogenous AMPs as therapeutic strategies against IBD is still at an early stage of development, augmented induction of endogenous AMPs may be another interesting future research direction for the protective and therapeutic purposes. This review discusses new advances in our understanding of how intestinal AMPs protect against pathogens and contribute to pathophysiology of IBD. (Intest Res 2014;12:20-33)
김정목 ( Jung Mogg Kim ) 대한소화기학회 2011 대한소화기학회지 Vol.58 No.6
Inflammatory bowel disease (IBD), the most important entities being ulcerative colitis and Crohn`s disease, are chronic, relapsing and remitting inflammatory conditions that result from chronic dysregulation of the mucosal immune system in the intestinal tract. Although the precise pathogenesis of IBD is still incompletely understood, increased levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-18 and tumor necrosis factor-α, are detected in active IBD and correlate with the severity of inflammation, indicating that these cytokines may play a key role in the development of IBD. Recently, the intracellular nucleotide- binding oligomerization domain-like receptor (NLR) family members, including NLRP1, NLRP3, NLRC4 and NLRP6, are emerging as important regulators of intestinal homeostasis. Together, one of those aforementioned molecules or the DNA sensor absent in melanoma 2 (AIM2), apoptosis-associated speck-like protein containing ``a caspase recruitment domain (CARD)`` (ASC) and caspase-1 form a large (>700 kDa) multi-protein complex called the inflammasome. Stimulation with specific microbial and endogenous molecules triggers inflammasome assembly and caspase-1 activation. Activated caspase-1 leads to the secretion of proinflammatory cytokines, including IL-1β and IL-18, and the promotion of pyroptosis, a form of phagocyte cell death induced by bacterial pathogens, in an inflamed tissue. Therefore, inflammasomes are assumed to mediate host defense against microbial pathogens and gut homeostasis, so that their dysregulation might contribute to IBD pathogenesis. This review focuses on recent advances of the role of NLRP3 inflammasome signaling in IBD pathogenesis. Improving knowledge of the inflammasome could provide insights into potential therapeutic targets for patients with IBD. (Korean J Gastroenterol 2011;58:300-310)
Kim, Jung Mogg,Kim, Joo Sung,Lee, Jin Young,Sim, Young-Suk,Kim, Young-Jeon,Oh, Yu-Kyoung,Yoon, Ho Joo,Kang, Ju Seop,Youn, Jeehee,Kim, Nayoung,Jung, Hyun Chae,Kim, Sunil WILEY-VCH Verlag 2010 European journal of immunology Vol.40 No.6
<P>Although Helicobacter pylori infections of the gastric mucosa are characterized by the infiltration of inflammatory cells such as eosinophils, the responses of eosinophils to H. pylori vacuolating cytotoxin (VacA) have not been fully elucidated. This study investigates the role of VacA in the apoptosis of human eosinophils. We treated human eosinophils with purified H. pylori VacA and observed that induction of apoptosis is a relatively late event. Expression of cellular inhibitor of apoptosis protein (c-IAP)-2 was upregulated during the early period of VacA stimulation, and transfection with c-IAP2 siRNA augmented apoptotic cell death. VacA caused the translocation of cytoplasmic Bax to the mitochondria and increased cytochrome c release from mitochondria in eosinophils. Transfection of an EoL-1 eosinophil cell line with Bax siRNA decreased the release of cytochrome c and DNA fragmentation. Furthermore, apoptosis facilitated by Bax and cytochrome c was primarily regulated by p38 MAPK in VacA-treated eosinophils. These results suggest that the exposure of human eosinophils to H. pylori VacA induces the early upregulation of c-IAP2 and a relatively late apoptotic response, with the apoptosis progressing through a sequential pathway that includes p38 MAPK activation, Bax translocation, and cytochrome c release.</P>
Distribution of fluoroquinolone MICs in <i>Helicobacter pylori</i> strains from Korean patients
Kim, Jung Mogg,Kim, Joo Sung,Kim, Nayoung,Jung, Hyun Chae,Song, In Sung Oxford University Press 2005 The Journal of antimicrobial chemotherapy Vol.56 No.5
<P><I>Objectives</I>: The aim of this study was to assess the prevalence rate of primary fluoroquinolone resistance in <I>Helicobacter pylori</I> isolates from Korean patients over the past 16 years.</P><P><I>Methods</I>: One hundred and thirty-five strains of <I>H. pylori</I> (34 strains in 1987, 36 in 1994 and 65 in 2003) were isolated from antral gastric mucosal biopsy specimens. The determination of MICs for the <I>H. pylori</I> isolates of ciprofloxacin, levofloxacin and moxifloxacin was examined by using the serial 2-fold agar dilution method. DNA sequences of the <I>gyrA</I> gene in fluoroquinolone-resistant strains were determined.</P><P><I>Results</I>: The distribution of fluoroquinolone MICs (ciprofloxacin, levofloxacin and moxifloxacin) shifted to higher concentrations during 1987–2003. All of the levofloxacin- or moxifloxacin-resistant strains were resistant to ciprofloxacin. Sequence analysis in fluoroquinolone-resistant strains showed point mutation of the <I>gyrA</I> gene at A272G and G271A, indicating mutations of the codon Asp-91 in the fluoroquinolone-resistance-determining region of the DNA gyrase.</P><P><I>Conclusions</I>: These results suggest that resistance to fluoroquinolones has been increasing in the Korean population and the resistance is most likely mediated through point mutation in <I>gyrA</I>.</P>
Kim, Jung Mogg,Kim, Su Hyun,Ko, Su Hyuk,Jung, Jireh,Chun, Jaeyoung,Kim, Nayoung,Jung, Hyun Chae,Kim, Joo Sung American Physiological Society 2013 American journal of physiology, Gastrointestinal a Vol.304 No.2
<P>Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.</P>
Helicobacter pylori 에 감염된 인체 위상피 세포에서의 cyclooxygenase - 2 의 발현 및 apoptosis
김정목(Jung Mogg Kim),김주성(Joo Sung Kim),정현채(Hyun Chae Jung),송인성(In Sung Song),김정룡(Chung Yong Kim) 대한내과학회 2002 대한내과학회지 Vol.62 No.2
N/A Background: Helicobacter pylori induces apoptosis and alters the proliferation of gastric mucosal epithelial cells. Cyclooxygenase-2 (COX-2) is an inducible form of COX for prostaglandin (PG) synthesis, which has been known to cause alteration in epithelial cell growth. In this study, we examined whether COX-2 gene expression by H. pylori infection could influence gastric epithelial cell apoptosis. Methods: Human gastric epithelial cells were infected with H. pylori, after which COX-2 gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (RT-PCR). The level of PGE2 was determined in culture supernatants by radioimmunoassay. Apoptosis and caspase-3 activation were also measured in H. pylori-infected gastric epithelial cells. Results: Expression of COX-2 mRNA and proteins was upregulated in Hs746T gastric epithelial cell lines infected with H. pylori, when assessed by quantitative RT-PCR and Western blot. However, COX-1 mRNA expression in H. pylori-infected Hs746T cells did not change. The extent of COX-2 mRNA expression and PGE2 production was similar in cagA-positive and cagA-negative strains and was not correlated with the presence of vacuolating cytotoxin. H. pylori infection resulted in apoptosis of gastric epithelial cell lines such as Hs746T. However, inhibition of COX-2 expression by NS-398, a specific COX-2 inhibitor, showed a significant increase of apoptosis and caspase-3 activation in Hs746T cells infected with H. pylori compared with H. pylori-infected cells without NS-398 treatment. In contrast, valerylsalicylate, an inhibitor that is relatively specific to COX-1, did not change the apoptosis levels of H. pylori-infected gastric epithelial cells. Conclusion: These results suggest that upregulated COX-2 expression by H. pylori infection can inhibit apoptosis of gastric epithelial cells.(Korean J Med 62:142-152, 2002)