title: Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice.
abstract: The hypothesis of this study was that cells of the monocyte/macrophage lineage (Mo/Mp) exhibit an impaired transition from pro-inflammatory to pro-healing phenotypes in wounds of diabetic mice, which contributes to deficient healing. Mo/Mp isolated from excisional wounds in non-diabetic db/+ mice exhibited a pro-inflammatory phenotype on day 5 post-injury, with high level expression of the pro-inflammatory molecules interleukin-1β, matrix metalloprotease-9 and inducible nitric oxide synthase. Wound Mo/Mp exhibited a less inflammatory phenotype on day 10 post-injury, with decreased expression of the pro-inflammatory molecules and increased expression of the alternative activation markers CD206 and CD36. In contrast, in db/db mice, the pro-inflammatory phenotype persisted through day 10 post-injury and was associated with reduced expression of insulin-like growth factor-1, transforming growth factor-β1 and vascular endothelial growth factor. Reduced levels of these growth factors in wounds of db/db mice may have contributed to impaired wound closure, reduced granulation tissue formation, angiogenesis and collagen deposition. The persistent pro-inflammatory wound Mo/Mp phenotype in db/db mice may have resulted from elevated levels of pro-inflammatory interleukin-1β and interferon-γ and reduced levels of anti-inflammatory interleukin-10 in the wound environment. Our findings are consistent with the hypothesis that dysregulation of Mo/Mp phenotypes contributes to impaired healing of diabetic wounds.
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Mirza
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koh
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014945:Wound Healing; D014947:Wounds and Injuries / Q000276:immunology*
chemical_list: D017931:DNA Primers