PMID- 16670522
OWN - NLM
STAT- MEDLINE
DCOM- 20061010
LR  - 20180913
IS  - 1078-0998 (Print)
IS  - 1078-0998 (Linking)
VI  - 12
IP  - 5
DP  - 2006 May
TI  - Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine 
      production in ulcerative colitis.
PG  - 339-45
AB  - BACKGROUND: We previously showed that Toll-like receptor-9 (TLR-9) ligands 
      ameliorate experimental colitis. In this study, we evaluated the effect of TLR-9 
      ligands on the generation of proinflammatory cytokines by human colonic mucosa. 
      MATERIALS AND METHODS: Colonoscopic biopsies were obtained from patients with 
      active ulcerative colitis (UC) and from normal subjects. The tissue was organ 
      cultured for 24 hours in the presence or absence of different types of 
      immunostimulatory (ISS) (CpG)-oligonucleotides (ODNs). Tumor necrosis 
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in the medium 
      were determined by enzyme-linked immunosorbent assay. RESULTS: In active UC, 
      hTNF-alpha and hIL-lbeta generation by inflamed colonic mucosa is 7- and 3-fold 
      higher, respectively, than their generation by normal mucosa. Class B CpG ODNs 
      inhibited colonic TNF-alpha and IL-1beta generation by 50%, whereas class A or C 
      ODNs had a partial or no effect, respectively. A novel class of ODNs that is 
      based on multiple TCG repeats was as effective as class B ODNs. This inhibition 
      resulted from the transcriptional suppression of IL-1beta that occurred within 
      the first 2 hours after ISS-ODN incubation. The addition of chloroquine abolished 
      the inhibitory effects of ISS-ODNs on colonic TNF-alpha and IL-1beta generation. 
      CONCLUSIONS: Only certain classes of ISS-ODNs inhibit the enhanced TNF-alpha and 
      IL-1beta generated ex vivo by inflamed colonic mucosa of patients with UC. The 
      effect of ISS-ODNs is mediated by triggering of TLR-9. These results suggest a 
      potential therapeutic value for ISS-ODNs in UC.
FAU - Rachmilewitz, Daniel
AU  - Rachmilewitz D
AD  - Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel. 
      tamid@netvision.net.il
FAU - Karmeli, Fanny
AU  - Karmeli F
FAU - Shteingart, Shimon
AU  - Shteingart S
FAU - Lee, Jongdae
AU  - Lee J
FAU - Takabayashi, Kenji
AU  - Takabayashi K
FAU - Raz, Eyal
AU  - Raz E
LA  - eng
GR  - AI40682/AI/NIAID NIH HHS/United States
GR  - DK35108/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Cytokines)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (TNF protein, human)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Colitis/*metabolism
MH  - Colitis, Ulcerative
MH  - Colon/*pathology
MH  - Cytokines/*metabolism
MH  - Female
MH  - Gastric Mucosa/*drug effects/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oligodeoxyribonucleotides/*pharmacology
MH  - Toll-Like Receptors/*agonists
MH  - Tumor Necrosis Factor-alpha
EDAT- 2006/05/04 09:00
MHDA- 2006/10/13 09:00
CRDT- 2006/05/04 09:00
PHST- 2006/05/04 09:00 [pubmed]
PHST- 2006/10/13 09:00 [medline]
PHST- 2006/05/04 09:00 [entrez]
AID - 00054725-200605000-00001 [pii]
AID - 10.1097/01.MIB.0000217335.30689.77 [doi]
PST - ppublish
SO  - Inflamm Bowel Dis. 2006 May;12(5):339-45. doi: 
      10.1097/01.MIB.0000217335.30689.77.