title: Negative pressure wound therapy inhibits inflammation and upregulates activating transcription factor-3 and downregulates nuclear factor-κB in diabetic patients with foot ulcerations.
abstract: Negative pressure wound therapy (NPWT) is one of the most important treatments for diabetic foot, but the underlying mechanisms of its benefits still remain elusive. This study aims to evaluate the inflammatory signals involved in the effects of negative pressure therapy on diabetic foot ulcers.
  
  
  
  We enrolled 22 patients with diabetic foot ulceration, 11 treated with NPWT and the other 11 treated with traditional debridement. All patients were treated and observed for 1 week. Granulation tissues were harvested and analyzed in both groups, and then were histologically and immunohistochemically analyzed. Enzyme-linked immunosorbent assay, Western blot analysis, and real-time PCR were performed to evaluate the expression of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB) p65, IkB-α, and activating transcription factor-3 (ATF-3).
  
  
  
  After 7 days of treatment, NPWT could obviously promote diabetic wound healing because of the mild inflammation and the dense cell-deposited matrix. Meanwhile, NPWT significantly decreased the expression of TNF-α, IL-6, and iNOS (all P < .05). The result of Western blotting and real-time PCR indicated that NPWT obviously decreased the level of IkB-α and NF-κB p65, and increased the level of ATF-3 (all P < .05).
  
  
  
  NPWT exerts an anti-inflammatory effect, possibly through the suppression of proinflammatory enzymes and cytokines resulting from IkB-α inhibition and ATF-3 activation, which may prevent the activation of the NF-κB pathway in human diabetic foot wounds.
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes, Shanghai Clinical Medical Center of Diabetes, Shanghai Key Clinical Center of Metabolic Diseases, Multidisciplinary Collaboration Group of Diabetic Foot, Shanghai Institute for Diabetes, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: R
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: J C
authors.initials: JC
authors.lastname: Mei
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Shao
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: H S
authors.initials: HS
authors.lastname: Wu
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Vascular Surgery, Shanghai Clinical Medical Center of Diabetes, Multidisciplinary Collaboration Center of Diabetic Foot, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital of Shanghai, Shanghai, China.
authors.forename: W C
authors.initials: WC
authors.lastname: Yan
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes, Shanghai Clinical Medical Center of Diabetes, Shanghai Key Clinical Center of Metabolic Diseases, Multidisciplinary Collaboration Group of Diabetic Foot, Shanghai Institute for Diabetes, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: L M
authors.initials: LM
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes, Shanghai Clinical Medical Center of Diabetes, Shanghai Key Clinical Center of Metabolic Diseases, Multidisciplinary Collaboration Group of Diabetic Foot, Shanghai Institute for Diabetes, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes, Shanghai Clinical Medical Center of Diabetes, Shanghai Key Clinical Center of Metabolic Diseases, Multidisciplinary Collaboration Group of Diabetic Foot, Shanghai Institute for Diabetes, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: W P
authors.initials: WP
authors.lastname: Jia
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000368:Aged; D017719:Diabetic Foot / Q000378:metabolism / Q000628:therapy*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D054843:Negative-Pressure Wound Therapy; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II
keywords: ATF-3; diabetic foot; inflammation; negative pressure wound therapy; nuclear factor-κB