PMID- 16009684
OWN - NLM
STAT- MEDLINE
DCOM- 20050809
LR  - 20181113
IS  - 0017-5749 (Print)
IS  - 1458-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 54
IP  - 8
DP  - 2005 Aug
TI  - Systemic administration of the chemokine macrophage inflammatory protein 1alpha 
      exacerbates inflammatory bowel disease in a mouse model.
PG  - 1114-20
AB  - INTRODUCTION: Exacerbations of inflammatory bowel disease are thought to be 
      related to concurrent infections. As infections are associated with elevated 
      local and serum concentrations of chemokines, we have determined whether systemic 
      administration of the CC chemokine macrophage inflammatory protein 1alpha 
      (MIP-1alpha) exacerbates colitis in a mouse model. METHODS: Colitis was induced 
      in Balb/c mice using trinitrobenzene sulfonic acid (TNBS). Starting four days 
      later, animals received daily intraperitoneal injections of recombinant 
      MIP-1alpha. On day 7, mice were killed and pieces of colon taken for 
      immunohistology and polymerase chain reaction analysis. The direct effects of 
      MIP-1alpha on mucosal T cells and fibroblasts in vitro were also investigated. 
      RESULTS: Systemic administration of MIP-1alpha markedly enhanced colitis with 
      mice developing large transmural ulcers filled with granulation tissue. Treatment 
      resulted in increased numbers of CD4 cells infiltrating the colonic lamina 
      propria, increased interferon gamma (IFN-gamma) levels, and increased transcripts 
      for tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 
      (MMP3). Isolated lamina propria lymphocytes from mice with TNBS colitis contained 
      increased numbers of IFN-gamma and TNF-alpha transcripts when stimulated with 
      MIP-1alpha in vitro. Colonic lamina propria fibroblasts also responded to 
      MIP-1alpha with increased proliferation and decreased collagen 1 synthesis but 
      fibroblast proliferation was not seen in vivo. CONCLUSIONS: These experiments 
      show that increasing serum concentrations of a chemokine, MIP-1alpha, exacerbates 
      immune mediated colitis. The effect seems to be due to the ability of MIP-1alpha 
      to boost Th1 responses in the gut wall. Our findings also suggest a potential 
      pathway by which peripheral infections can exacerbate inflammatory bowel disease.
FAU - Pender, S L-F
AU  - Pender SL
AD  - Division of Infection, Inflammation, and Repair, University of Southampton School 
      of Medicine, UK
FAU - Chance, V
AU  - Chance V
FAU - Whiting, C V
AU  - Whiting CV
FAU - Buckley, M
AU  - Buckley M
FAU - Edwards, M
AU  - Edwards M
FAU - Pettipher, R
AU  - Pettipher R
FAU - MacDonald, T T
AU  - MacDonald TT
LA  - eng
PT  - Journal Article
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Colitis, Ulcerative/*immunology
MH  - Colon/immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Fibroblasts/immunology
MH  - Immunohistochemistry/methods
MH  - Injections, Intraperitoneal
MH  - Interferon-gamma/analysis
MH  - Intestinal Mucosa/immunology
MH  - Macrophage Inflammatory Proteins/*administration & dosage
MH  - Matrix Metalloproteinase 3/analysis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Tumor Necrosis Factor-alpha/analysis
PMC - PMC1774881
EDAT- 2005/07/13 09:00
MHDA- 2005/08/10 09:00
PMCR- 2008/08/01
CRDT- 2005/07/13 09:00
PHST- 2005/07/13 09:00 [pubmed]
PHST- 2005/08/10 09:00 [medline]
PHST- 2005/07/13 09:00 [entrez]
PHST- 2008/08/01 00:00 [pmc-release]
AID - 54/8/1114 [pii]
AID - 0541114 [pii]
AID - 10.1136/gut.2004.052779 [doi]
PST - ppublish
SO  - Gut. 2005 Aug;54(8):1114-20. doi: 10.1136/gut.2004.052779.