title: CCL2 (pM levels) as a therapeutic agent in Inflammatory Bowel Disease models in mice.
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.
authors.affiliation: Department of Immunology, the Weizmann Institute of Science, Rehovot, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Maharshak
authors.forename: G
authors.initials: G
authors.lastname: Hart
authors.forename: E
authors.initials: E
authors.lastname: Ron
authors.forename: E
authors.initials: E
authors.lastname: Zelman
authors.forename: A
authors.initials: A
authors.lastname: Sagiv
authors.forename: N
authors.initials: N
authors.lastname: Arber
authors.forename: E
authors.initials: E
authors.lastname: Brazowski
authors.forename: R
authors.initials: R
authors.lastname: Margalit
authors.forename: E
authors.initials: E
authors.lastname: Elinav
authors.forename: I
authors.initials: I
authors.lastname: Shachar
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D002273:Carcinogens; D018932:Chemokine CCL2; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D001397:Azoxymethane