PMID- 20937806
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20240322
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 50
DP  - 2010 Dec 10
TI  - Tumor necrosis factor alpha-induced inflammation is increased but apoptosis is 
      inhibited by common food additive carrageenan.
PG  - 39511-22
LID - 10.1074/jbc.M110.159681 [doi]
AB  - Tumor necrosis factor (TNF)-alpha, a homotrimeric, pleiotropic cytokine, is secreted 
      in response to inflammatory stimuli in diseases such as rheumatoid arthritis and 
      inflammatory bowel disease. TNF-alpha mediates both apoptosis and inflammation, 
      stimulating an inflammatory cascade through the non-canonical pathway of NF-kappaB 
      activation, leading to increased nuclear RelB and p52. In contrast, the common 
      food additive carrageenan (CGN) stimulates inflammation through both the 
      canonical and non-canonical pathways of NF-kappaB activation and utilizes the adaptor 
      molecule BCL10 (B-cell leukemia/lymphoma 10). In a series of experiments, colonic 
      epithelial cells and mouse embryonic fibroblasts were treated with TNF-alpha and 
      carrageenan in order to simulate the possible effects of exposure to dietary CGN 
      in the setting of a TNF-alpha-mediated inflammatory disease process. A marked 
      increase in secretion of IL-8 occurred, attributable to synergistic effects on 
      phosphorylated NF-kappaB-inducing kinase (NIK) in the non-canonical pathway. TNF-alpha 
      induced the ubiquitination of TRAF2 (TNF receptor-associated factor 2), which 
      interacts with NIK, and CGN induced phosphorylation of BCL10, leading to 
      increased NIK phosphorylation. These results suggest that TNF-alpha and CGN in 
      combination act to increase NIK phosphorylation, thereby increasing activation of 
      the non-canonical pathway of NF-kappaB activation. In contrast, the apoptotic effects 
      of TNF-alpha, including activation of caspase-8 and PARP-1 (poly(ADP-ribose) 
      polymerase 1) fragmentation, were markedly reduced in the presence of CGN, and 
      CGN caused reduced expression of Fas. These findings demonstrate that exposure to 
      CGN drives TNF-alpha-stimulated cells toward inflammation rather than toward 
      apoptotic cell death and suggest that CGN exposure may compromise the 
      effectiveness of anti-TNF-alpha therapy.
FAU - Bhattacharyya, Sumit
AU  - Bhattacharyya S
AD  - Department of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
FAU - Dudeja, Pradeep K
AU  - Dudeja PK
FAU - Tobacman, Joanne K
AU  - Tobacman JK
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101011
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (B-Cell CLL-Lymphoma 10 Protein)
RN  - 0 (Bcl10 protein, mouse)
RN  - 0 (Food Additives)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (Leupeptins)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 9000-07-1 (Carrageenan)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - *Apoptosis
MH  - B-Cell CLL-Lymphoma 10 Protein
MH  - Carrageenan/*pharmacology
MH  - Fibroblasts/metabolism
MH  - Food Additives/chemistry
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Inflammation
MH  - Interleukin-8/metabolism
MH  - Leupeptins/pharmacology
MH  - Mice
MH  - NF-KappaB Inhibitor alpha
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - NF-kappaB-Inducing Kinase
PMC - PMC2998126
EDAT- 2010/10/13 06:00
MHDA- 2011/01/11 06:00
PMCR- 2011/12/10
CRDT- 2010/10/13 06:00
PHST- 2010/10/13 06:00 [entrez]
PHST- 2010/10/13 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
PHST- 2011/12/10 00:00 [pmc-release]
AID - S0021-9258(20)60647-0 [pii]
AID - M110.159681 [pii]
AID - 10.1074/jbc.M110.159681 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Dec 10;285(50):39511-22. doi: 10.1074/jbc.M110.159681. Epub 
      2010 Oct 11.