title: Localized delivery of dexamethasone-21-phosphate via microdialysis implants in rat induces M(GC) macrophage polarization and alters CCL2 concentrations.
abstract: Microdialysis sampling probes were implanted into the subcutaneous space on the dorsal side of male Sprague Dawley rats to locally deliver dexamethasone-21-phosphate (Dex) with the aim of altering in vivo macrophage polarization. Macrophage polarization is of significant interest in the field of biomaterials since wound-healing macrophages are a possible means to extend implant life as well as improve tissue remodeling to an implant. Quantitative analysis of CCL2 in collected dialysates, gene expression and immunohistochemistry performed on the tissue surrounding the microdialysis implant were used to evaluate if Dex polarized macrophages. Dex infusion down-regulated IL-6 and CCL2 gene expression and decreased CCL2 concentrations in dialysates collected at the implant site. Dex appeared to have no significant effect on the gene regulation of CD163, a commonly used M2c macrophage surface marker; Arg2; and iNOS2. However, Dex infusion was effective at increasing the number of CD163(+) cells surrounding the implanted microdialysis probe. This work demonstrates the use of microdialysis sampling to deliver agents such as Dex to alter macrophage polarization in vivo while allowing the ability to collect cytokines in the surrounding microenvironment.
authors.affiliation: Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Keeler
authors.affiliation: Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA; Department of Biological Sciences, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Durdik
authors.affiliation: Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA. Electronic address: jstenken@uark.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stenken
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017551:Microdialysis; D016133:Polymerase Chain Reaction; D051381:Rats
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone
keywords: CCL2 (MCP-1, monocyte chemotactic protein-1); Dexamethasone; Macrophage polarization; Rat; qRT-PCR