PMID- 11849320
OWN - NLM
STAT- MEDLINE
DCOM- 20020304
LR  - 20240109
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 105
IP  - 1
DP  - 2002 Jan
TI  - Epithelial cells respond to proteolytic and non-proteolytic detachment by 
      enhancing interleukin-6 responses.
PG  - 101-10
AB  - Intestinal inflammatory disease or infection often results in the loss of the 
      epithelial layer as a result mainly of the action of proteases, including the 
      leucocyte serine proteinases (neutrophil elastase), lysosomal cathepsins and the 
      matrix metalloproteinases from recruited inflammatory cells. Previous studies 
      have shown that bronchial or intestinal epithelial cells (IEC) can respond to 
      proteolytic attack by producing cytokines. In this study, we have determined the 
      effect of protease treatment on interleukin-6 (IL-6) and monocyte chemoattractant 
      protein-1 (MCP-1) production by IEC lines. Both neutrophil elastase and trypsin 
      treatment induced elevated levels of mRNA for IL-6 in rat IEC-6 cells. 
      Non-proteolytic detachment of the IEC-6 cells also induced elevated levels of 
      IL-6 mRNA, suggesting that the effect was not caused by a specific protease or 
      degradation product, but probably by an effect on cell shape or cell detachment. 
      Similar results were seen with the IEC-18 cell line. Trypsin treatment of the 
      IEC-6 cells also enhanced unstimulated and IL-1 beta costimulated IL-6 secretion, 
      but not MCP-1 secretion or mRNA levels. Finally, nuclear levels of the 
      CCAAT/enhancer binding protein-beta (C/EBP-beta) were rapidly enhanced after 
      proteolytic detachment of the IEC-6 cells, suggesting a mechanism for the 
      enhancement of IL-6 mRNA responses. These data indicate that epithelial cells can 
      respond to proteolytic attack or cell detachment by producing IL-6, a cytokine 
      with several anti-inflammatory and antiprotease effects, which may be important 
      in moderating the loss of the epithelial layer by its effects on nearby 
      epithelial or inflammatory cells.
FAU - Miller, Tabbi L
AU  - Miller TL
AD  - Department of Biological Sciences, Binghamton University (SUNY), Binghamton, New 
      York 13902-6000, USA.
FAU - McGee, Dennis W
AU  - McGee DW
LA  - eng
GR  - R15 DK054049/DK/NIDDK NIH HHS/United States
GR  - DK 54049/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Ddit3 protein, rat)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - EC 3.4.21.4 (Trypsin)
SB  - IM
MH  - Animals
MH  - Blotting, Western/methods
MH  - CCAAT-Enhancer-Binding Proteins/physiology
MH  - Cell Survival
MH  - Chemokine CCL2/physiology
MH  - Endopeptidases/*physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial Cells/*immunology
MH  - In Situ Nick-End Labeling
MH  - Interleukin-1/physiology
MH  - Interleukin-6/*physiology
MH  - Intestinal Mucosa/*cytology/immunology
MH  - Leukocyte Elastase/physiology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factor CHOP
MH  - Transcription Factors/physiology
MH  - Trypsin/physiology
PMC - PMC1782634
EDAT- 2002/02/19 10:00
MHDA- 2002/03/05 10:01
PMCR- 2003/01/01
CRDT- 2002/02/19 10:00
PHST- 2002/02/19 10:00 [pubmed]
PHST- 2002/03/05 10:01 [medline]
PHST- 2002/02/19 10:00 [entrez]
PHST- 2003/01/01 00:00 [pmc-release]
AID - 1352 [pii]
AID - 10.1046/j.0019-2805.2001.01352.x [doi]
PST - ppublish
SO  - Immunology. 2002 Jan;105(1):101-10. doi: 10.1046/j.0019-2805.2001.01352.x.