title: Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response.
abstract: Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older), and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif) ligand 2 (CCL2) expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds.
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wood
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Jayaraman
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America; Rush University Cancer Center, Rush University Medical Center, Chicago, Illinois, United States of America; Developmental Center for AIDS Research, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Huelsmann
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America; Department of Dermatology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Bonish
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Derick
authors.initials: D
authors.lastname: Burgad
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Sivaramakrishnan
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qin
authors.affiliation: Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Luisa A
authors.initials: LA
authors.lastname: DiPietro
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America; Rush University Cancer Center, Rush University Medical Center, Chicago, Illinois, United States of America; Developmental Center for AIDS Research, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America; Rush University Cancer Center, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Sasha H
authors.initials: SH
authors.lastname: Shafikhani
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism* / Q000494:pharmacology; D048909:Diabetes Complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2; D004195:Disease Models, Animal; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology
chemical_list: D018932:Chemokine CCL2