PMID- 22144489
OWN - NLM
STAT- MEDLINE
DCOM- 20120327
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 80
IP  - 2
DP  - 2012 Feb
TI  - Distinct compartmentalization of NF-kappaB activity in crypt and crypt-denuded lamina 
      propria precedes and accompanies hyperplasia and/or colitis following bacterial 
      infection.
PG  - 753-67
LID - 10.1128/IAI.06101-11 [doi]
AB  - Citrobacter rodentium induces transmissible murine colonic hyperplasia (TMCH) and 
      variable degrees of inflammation and necrosis depending upon the genetic 
      background. Utilizing C. rodentium-induced TMCH in C3H/HeNHsd inbred mice, we 
      observed significant crypt hyperplasia on days 3 and 7 preceding active colitis. 
      NF-kappaB activity in the crypt-denuded lamina propria (CLP) increased within 24 h 
      postinfection, followed by its activation in the crypts at day 3, which peaked by 
      day 7. Increases in interleukin-alpha1 (IL-1alpha), IL-12(p40), and macrophage 
      inflammatory protein 1alpha (MIP-1alpha) paralleled NF-kappaB activation, while increases in 
      IL-1alpha/beta, IL-6/IL-12(p40)/granulocyte colony-stimulating factor 
      (G-CSF)/keratinocyte-derived chemokine (KC)/monocyte chemotactic protein 1 
      (MCP-1), and MIP-1alpha followed NF-kappaB activation leading to significant recruitment 
      of neutrophils to the colonic mucosa and increased colonic myeloperoxidase (MPO) 
      activity. Phosphorylation of the crypt cellular and nuclear p65 subunit at 
      serines 276 and 536 led to functional NF-kappaB activation that facilitated 
      expression of its downstream target, CXCL-1/KC, during TMCH. Distinct 
      compartmentalization of phosphorylated extracellular signal-regulated kinase 1 
      and 2 ([ERK1/2] Thr(180)/Tyr(182)) and p38 (Thr(202)/Tyr(204)) in the CLP 
      preceded increases in the crypts. Inhibition of ERK1/2 and p38 suppressed NF-kappaB 
      activity in both crypts and the CLP. Dietary administration of 6% pectin or 4% 
      curcumin in C. rodentium-infected mice also inhibited NF-kappaB activity and blocked 
      CD3, F4/80, IL-1alpha/beta, G-CSF/MCP-1/KC, and MPO activity in the CLP while not 
      affecting NF-kappaB activity in the crypts. Thus, distinct compartmentalization of 
      NF-kappaB activity in the crypts and the CLP regulates crypt hyperplasia and/or 
      colitis, and dietary intervention may be a novel strategy to modulate 
      NF-kappaB-dependent protective immunity to facilitate crypt regeneration following C. 
      rodentium-induced pathogenesis.
FAU - Chandrakesan, Parthasarathy
AU  - Chandrakesan P
AD  - Department of Internal Medicine, Division of Digestive Diseases and Nutrition, 
      University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
FAU - Ahmed, Ishfaq
AU  - Ahmed I
FAU - Chinthalapally, Anisha
AU  - Chinthalapally A
FAU - Singh, Pomila
AU  - Singh P
FAU - Awasthi, Shanjana
AU  - Awasthi S
FAU - Anant, Shrikant
AU  - Anant S
FAU - Umar, Shahid
AU  - Umar S
LA  - eng
GR  - R01 CA097959/CA/NCI NIH HHS/United States
GR  - R01 CA109269/CA/NCI NIH HHS/United States
GR  - R01 CA131413/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111205
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Citrobacter rodentium
MH  - Colitis/*etiology/*pathology
MH  - Cytokines/genetics/metabolism
MH  - Diet
MH  - Enterobacteriaceae Infections/microbiology/*pathology
MH  - Female
MH  - Gene Expression Regulation
MH  - Hyperplasia/*pathology
MH  - Intestinal Mucosa/microbiology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mucous Membrane/microbiology/*pathology
MH  - NF-kappa B/genetics/*metabolism
MH  - Peroxidase/metabolism
PMC - PMC3264290
EDAT- 2011/12/07 06:00
MHDA- 2012/03/28 06:00
PMCR- 2012/08/01
CRDT- 2011/12/07 06:00
PHST- 2011/12/07 06:00 [entrez]
PHST- 2011/12/07 06:00 [pubmed]
PHST- 2012/03/28 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - IAI.06101-11 [pii]
AID - 6101-11 [pii]
AID - 10.1128/IAI.06101-11 [doi]
PST - ppublish
SO  - Infect Immun. 2012 Feb;80(2):753-67. doi: 10.1128/IAI.06101-11. Epub 2011 Dec 5.