title: Monocyte Chemotactic Protein-1-Interleukin-6-Osteopontin Pathway of Intra-Aneurysmal Tissue Healing.
abstract: We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via an MCP-1-releasing poly(lactic-co-glycolic acid)-coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin are downstream mediators in the MCP-1-mediated aneurysm-healing pathway.
  
  
  
  Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6, and osteopontin) and control poly(lactic-co-glycolic acid) coils were created and then implanted into the aneurysms to evaluate their intra-aneurismal-healing capacity. To investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and osteopontin were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data.
  
  
  
  We observed increased expression of IL-6 in MCP-1-coil-treated aneurysms and not in control-poly(lactic-co-glycolic acid)-only-treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to osteopontin. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of osteopontin to murine carotid aneurysms via osteopontin-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, osteopontin expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits osteopontin expression in MCP-1-mediated aneurysm healing.
  
  
  
  Our findings suggest that IL-6 and osteopontin are key downstream mediators of MCP-1-mediated intra-aneurysmal healing.
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville. koji@ufl.edu.
authors.forename: Koji
authors.initials: K
authors.lastname: Hosaka
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Kelley
authors.initials: K
authors.lastname: Rojas
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Hanain Z
authors.initials: HZ
authors.lastname: Fazal
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Matheus B
authors.initials: MB
authors.lastname: Schneider
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Jorma
authors.initials: J
authors.lastname: Shores
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Vincent
authors.initials: V
authors.lastname: Federico
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Matthew
authors.initials: M
authors.lastname: McCord
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: From the Department of Neurosurgery, University of Florida, Gainesville.
authors.forename: Brian
authors.initials: B
authors.lastname: Hoh
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism*; D001672:Biocompatible Materials / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D002532:Intracranial Aneurysm / Q000188:drug therapy / Q000628:therapy*; D019344:Lactic Acid / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000008:administration & dosage / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D019138:Antibodies, Blocking; D001672:Biocompatible Materials; D018932:Chemokine CCL2; D015850:Interleukin-6; D053495:Osteopontin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: antibodies, blocking; interleukins; intracranial aneurysm; monocyte chemoattractant protein-1; osteopontin