CCL2 (pM levels) as a therapeutic agent in inflammatory bowel disease models in mice

N. Maharshak, G. Hart, E. Ron, E. Zelman, A. Sagiv, N. Arber, E. Brazowski, R. Margalit, E. Elinav, I. Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Chemokines regulate the pathways that restrict homing of specific subsets of immune cells, and thereby fine tune the immune response at specific lymphoid and peripheral tissues. CCL2 is a chemokine that induces migration of monocytes, memory T cells, and dendritic cells. Previously, we demonstrated that pM levels of CCL2 dramatically inhibit migration of T cells. The aim was to test whether subphysiological doses of CCL2 can ameliorate murine colitis and inflammation-induced colorectal cancer. Methods: TNBS (2,4,6 trinitrobenzene sulfonic acid) colitis and dextran sodium sulfate (DSS) colitis were induced in Balb/c and C57BL/6 mice, respectively. Mice were treated daily with intraperitoneal CCL2 injections. Disease activity was assessed clinically, histologically, and by measuring inflammatory cytokine levels. In addition, an inflammatory cancer model was induced by azoxymethane-DSS (AOM-DSS) in Balb/c mice. Mice were treated daily with CCL2 for 11 weeks and then assessed for number of tumors in the colons. Results: Daily administration of CCL2 (60-120 ng) significantly decreased the development of TNBS- and DSS-induced colitis. In a DSS-AOM model, CCL2-treated mice developed significantly fewer tumors (P < 0.005) at 11 weeks. Chronic inflammation in the CCL2-treated mice was significantly less pronounced as compared to phosphate-buffered saline-treated mice. Conclusions: Administration of pM levels of CCL2 significantly inhibits migration of T cells in amelioration of TNBS and DSS colitis and inhibits development of colorectal cancer in an AOM-DSS colitis model in mice. Thus, pM levels of CCL2 may be clinically beneficial as an antiinflammatory agent in IBD.

Original languageEnglish
Pages (from-to)1496-1504
Number of pages9
JournalInflammatory Bowel Diseases
Volume16
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • CCL2
  • Colorectal cancer
  • Inflammatory bowel disease
  • Murine colitis models

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