PMID- 9536945
OWN - NLM
STAT- MEDLINE
DCOM- 19980420
LR  - 20190501
IS  - 0017-5749 (Print)
IS  - 1458-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 42
IP  - 2
DP  - 1998 Feb
TI  - Interferon gamma induces differential upregulation of alpha and beta chemokine 
      secretion in colonic epithelial cell lines.
PG  - 208-13
AB  - BACKGROUND: Production of chemoattractant factors by the intestinal epithelium 
      may contribute to mucosal infiltration by inflammatory cells in inflammatory 
      bowel disease. Secretion of the alpha chemokine interleukin 8 (IL-8), a 
      neutrophil chemoattractant, has been widely studied, but little is known about 
      epithelial secretion of beta chemokines, which are preferentially involved in 
      recruiting monocytes. AIMS: To investigate the profiles of alpha and beta 
      chemokine secretion in colonic cell lines and their differential modulation by 
      interferon gamma (IFN-gamma), a product of activated T lymphocytes and natural 
      killer cells. METHODS AND RESULTS: HT29-19A, a model of the CT secretory crypt 
      cell, exhibited a parallel secretion of the alpha chemokines IL-8 and GRO alpha, 
      which could be markedly upregulated by tumour necrosis factor alpha (TNF-alpha) 
      and IL-1 beta. These cells showed no significant expression of the beta 
      chemokines RANTES (regulated upon activation T cell expressed and secreted), 
      MIP-1 alpha (macrophage inflammatory protein 1 alpha), and MCP-1 (monocyte 
      chemotactic protein 1) under these conditions, but IFN-gamma in combination with 
      TNF-alpha caused a dose dependent induction of RANTES and MCP-1 secretion. This 
      was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-gamma had 
      no significant effect on TNF-alpha stimulated IL-8 secretion. Caco-2 cells, with 
      features more typical of villus absorptive cells, were relatively poor secretors 
      of alpha chemokines but secreted high levels of MCP-1 in response to IL-1 beta. 
      IFN-gamma did not influence alpha or beta chemokine secretion in these cells. 
      CONCLUSIONS: These studies suggest that intestinal epithelial cells may produce 
      chemokines capable of attracting both neutrophils and monocytes. The ability of 
      IFN-gamma to activate the expression of beta chemokines preferentially could 
      facilitate the development of chronic inflammatory infiltrates.
FAU - Warhurst, A C
AU  - Warhurst AC
AD  - Department of Surgery, Hope Hospital, Salford, UK.
FAU - Hopkins, S J
AU  - Hopkins SJ
FAU - Warhurst, G
AU  - Warhurst G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (CXCL1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Growth Substances)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Caco-2 Cells/*drug effects/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL5/genetics/metabolism
MH  - Chemokine CXCL1
MH  - Chemokines/*metabolism
MH  - *Chemokines, CXC
MH  - Chemotactic Factors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Gene Expression
MH  - Growth Inhibitors/metabolism
MH  - Growth Substances/metabolism
MH  - HT29 Cells/*drug effects/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-8/metabolism
MH  - RNA, Messenger/analysis
MH  - Stimulation, Chemical
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC1726988
EDAT- 1998/04/16 00:00
MHDA- 1998/04/16 00:01
PMCR- 2001/02/01
CRDT- 1998/04/16 00:00
PHST- 1998/04/16 00:00 [pubmed]
PHST- 1998/04/16 00:01 [medline]
PHST- 1998/04/16 00:00 [entrez]
PHST- 2001/02/01 00:00 [pmc-release]
AID - 10.1136/gut.42.2.208 [doi]
PST - ppublish
SO  - Gut. 1998 Feb;42(2):208-13. doi: 10.1136/gut.42.2.208.