PMID- 17353291
OWN - NLM
STAT- MEDLINE
DCOM- 20070614
LR  - 20220316
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 75
IP  - 5
DP  - 2007 May
TI  - Deficiencies of myeloid differentiation factor 88, Toll-like receptor 2 (TLR2), 
      or TLR4 produce specific defects in macrophage cytokine secretion induced by 
      Helicobacter pylori.
PG  - 2408-14
AB  - Helicobacter pylori is a gram-negative microaerophilic bacterium that colonizes 
      the gastric mucosa, leading to disease conditions ranging from gastritis to 
      cancer. Toll-like receptors (TLRs) play a central role in innate immunity by 
      their recognition of conserved molecular patterns on bacteria, fungi, and 
      viruses. Upon recognition of microbial components, these TLRs associate with 
      several adaptor molecules, including myeloid differentiation factor 88 (MyD88). 
      To investigate the contribution of the innate immune system to H. pylori 
      infection, bone marrow-derived macrophages from mice deficient in TLR2, TLR4, 
      TLR9, and MyD88 were infected with H. pylori SS1 and SD4 for 24 or 48 h. We 
      demonstrate that MyD88 was essential for H. pylori induction of all cytokines 
      investigated except alpha interferon (IFN-alpha). The secretion of IFN-alpha was 
      substantially increased from cells deficient in MyD88. H. pylori induced 
      interleukin-12 (IL-12) and IL-10 through TLR4/MyD88 signaling. In addition, H. 
      pylori induced less IL-6 and IL-1beta in TLR2-deleted macrophages, suggesting 
      that the MyD88 pathway activated by TLR2 stimulation is responsible for H. pylori 
      induction of the host proinflammatory response (IL-6 and IL-1beta). These 
      observations are important in light of a recent report on IL-6 and IL-1beta 
      playing a role in the development of H. pylori-related gastric cancer. In 
      conclusion, our study demonstrates that H. pylori activates TLR2 and TLR4, 
      leading to the secretion of distinct cytokines by macrophages.
FAU - Obonyo, Marygorret
AU  - Obonyo M
AD  - School of Medicine, Department of Medicine, University of California, San Diego, 
      9500 Gilman Drive, La Jolla, CA 92093-0640, USA. mobonyo@ucsd.edu
FAU - Sabet, Mojgan
AU  - Sabet M
FAU - Cole, Sheri P
AU  - Cole SP
FAU - Ebmeyer, Joerg
AU  - Ebmeyer J
FAU - Uematsu, Satoshi
AU  - Uematsu S
FAU - Akira, Shizuo
AU  - Akira S
FAU - Guiney, Donald G
AU  - Guiney DG
LA  - eng
GR  - K01 CA096709/CA/NCI NIH HHS/United States
GR  - K01 CA96709/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070312
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Cytokines)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Cells, Cultured
MH  - Cytokines/*metabolism
MH  - Helicobacter pylori/*pathogenicity
MH  - Humans
MH  - Macrophages/immunology/*microbiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Myeloid Differentiation Factor 88/deficiency/genetics/metabolism
MH  - *Toll-Like Receptor 2/deficiency/genetics/metabolism
MH  - *Toll-Like Receptor 4/deficiency/genetics/metabolism
PMC - PMC1865764
EDAT- 2007/03/14 09:00
MHDA- 2007/06/15 09:00
PMCR- 2007/09/01
CRDT- 2007/03/14 09:00
PHST- 2007/03/14 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/03/14 09:00 [entrez]
PHST- 2007/09/01 00:00 [pmc-release]
AID - IAI.01794-06 [pii]
AID - 1794-06 [pii]
AID - 10.1128/IAI.01794-06 [doi]
PST - ppublish
SO  - Infect Immun. 2007 May;75(5):2408-14. doi: 10.1128/IAI.01794-06. Epub 2007 Mar 
      12.