Human β-Defensin 3 Peptide Is Increased and Redistributed in Crohn's Ileitis

被引:27
作者
Meisch, Jeffrey P. [1 ]
Nishimura, Michiko [2 ,3 ]
Vogel, Ryan M. [1 ]
Sung, Hannah C. [1 ]
Bednarchik, Beth A. [1 ]
Ghosh, Santosh K. [3 ]
Fu, Pingfu [4 ]
McCormick, Thomas [5 ]
Weinberg, Aaron [3 ]
Levine, Alan D. [1 ,3 ,6 ,7 ,8 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA
[2] Hlth Sci Univ Hokkaido, Dept Clin Oral Pathol, Sch Dent, Ishikari Tohbetsu, Hokkaido, Japan
[3] Case Western Reserve Univ, Dept Biol Sci, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Dept Biostat, Cleveland, OH 44106 USA
[5] Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA
[6] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA
[7] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
[8] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA
关键词
beta-defensins; inflammatory bowel disease; Crohn's disease; immunomodulation; epithelium; innate immunity; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; HUMAN BETA-DEFENSIN-3; ANTIMICROBIAL PEPTIDES; IMMUNE HOMEOSTASIS; ULCERATIVE-COLITIS; ALPHA-DEFENSINS; INNATE IMMUNITY; MESSENGER-RNA; PANETH CELLS;
D O I
10.1097/MIB.0b013e318280b11a
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Antimicrobial peptides (AMPs) maintain a sterile environment in intestinal crypts, limiting microbial colonization and invasion. Decreased AMP expression is proposed to increase the risk for inflammatory bowel disease. Expression and function of inducible AMPs, human beta-defensin 2 and 3 (hBD-2 and hBD-3), remain poorly characterized in healthy and chronically inflamed intestine. Methods: Peptide concentrations of hBD-2 and hBD-3 in serum and intestinal biopsies of subjects with ulcerative colitis and Crohn's disease (CD), and those of healthy subjects were measured by ELISA. Messenger RNA of hBD-2 and hBD-3 was quantified by quantitative PCR in biopsies from the terminal ileum (TI) of patients with CD and healthy controls. Peptide localization of hBD-3 in the TI was visualized by confocal microscopy. Results: Immunoreactive hBD-3 peptide is present in the TI and colon in healthy subjects. In the TI of patients with CD, hBD-3, but not hBD-2 peptide, is increased 4-fold, whereas hBD-2 peptide is elevated in the serum. Messenger RNA of hBD-3 in the CD TI remains unchanged and does not correlate with hBD-3 peptide expression. However, hBD-3 is localized to Paneth cell granules and the apical surface of the healthy columnar epithelium. In CD, hBD-3 peptide location switches to the basolateral surface of the columnar epithelium and is diffusely distributed within the lamina propria. Conclusion: The peptide hBD-3 throughout the healthy gastrointestinal tract suggests a role in maintaining balance between host defenses and commensal microbiota. Increased and relocalized secretion of hBD-3 toward the lamina propria in the CD TI indicates possible local immunomodulation during chronic inflammation, whereas increased serum hBD-2 in CD implicates its systemic antimicrobial and immunomodulatory role.
引用
收藏
页码:942 / 953
页数:12
相关论文
共 47 条
[1]   IL-4 and IL-13 negatively regulate TNF-α- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3 [J].
Albanesi, Cristina ;
Fairchild, Heather R. ;
Madonna, Stefania ;
Scarponi, Claudia ;
De Pita, Ornella ;
Leung, Donald Y. M. ;
Howell, Michael D. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (02) :984-992
[2]   Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut [J].
Artis, David .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (06) :411-420
[3]   Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria [J].
Ayabe, T ;
Satchell, DP ;
Wilson, CL ;
Parks, WC ;
Selsted, ME ;
Ouellette, AJ .
NATURE IMMUNOLOGY, 2000, 1 (02) :113-118
[4]   IL-6 and IL-12 specifically regulate the expression of Rab5 and Rab7 via distinct signaling pathways [J].
Bhattacharya, Malavika ;
Ojha, Namrata ;
Solanki, Sunil ;
Mukhopadhyay, Chinmay K. ;
Madan, Richa ;
Patel, Nitin ;
Krishnamurthy, Ganga ;
Kumar, Senthil ;
Basu, Sandip K. ;
Mukhopadhyay, Amitabha .
EMBO JOURNAL, 2006, 25 (12) :2878-2888
[5]   The immunological and genetic basis of inflammatory bowel disease [J].
Bouma, G ;
Strober, W .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (07) :521-533
[6]   IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration [J].
Brand, S ;
Beigel, F ;
Olszak, T ;
Zitzmann, K ;
Eichhorst, ST ;
Otte, JM ;
Diepolder, H ;
Marquardt, A ;
Jagla, W ;
Popp, A ;
Leclair, S ;
Herrmann, K ;
Seiderer, J ;
Ochsenkühn, T ;
Göke, B ;
Auernhammer, CJ ;
Dambacher, J .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2006, 290 (04) :G827-G838
[7]  
Duchmann R, 1995, CLIN EXP IMMUNOL, V102, P448
[8]   Immune Responses to the Microbiota at the Intestinal Mucosal Surface [J].
Duerkop, Breck A. ;
Vaishnava, Shipra ;
Hooper, Lora V. .
IMMUNITY, 2009, 31 (03) :368-376
[9]   Expression of β-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells [J].
Duits, LA ;
Ravensbergen, B ;
Rademaker, M ;
Hiemstra, PS ;
Nibbering, PH .
IMMUNOLOGY, 2002, 106 (04) :517-525
[10]   β-Defensin-3 and -4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis [J].
Fahlgren, A ;
Hammarström, S ;
Danielsson, Å ;
Hammarström, ML .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2004, 137 (02) :379-385