Expression of inducible nitric oxide synthase in human burn wounds

Paulsen, Stephen M.; Wurster, Samuel H.; Nanney, Lillian B.

doi:10.1046/j.1524-475x.1998.60208.x

Cited by 47 publications

(29 citation statements)

References 8 publications

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“…In biopsy samples of human burn wounds, immunohistochemical staining for iNOS demonstrated increased levels for 4À21 days after burn injury. This contrasted to negligible levels of iNOS from biopsies of normal skin (Paulsen et al, 1998). Dermal injection of histamine (a mediator of inflammatory responses) led to increased local NO and cGMP levels, as measured by microdialysis in human skin.…”

Section: Wound and Tissue Responses To Nitric Oxidementioning

confidence: 85%

Nitric oxide in wound-healing

et al. 2005

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Modulation of the complex process of wound-healing remains a surgical challenge. Little improvement beyond controlling infection, gentle tissue handling, and debridement of necrotic tissue has been had in the modern era. However, increasing appreciation of the process from a biomolecular perspective offers the potential for making significant strides in wound modulation. The bioactive molecule nitric oxide was found to have wide-ranging impact on cellular activities, including the cellular responses engendered by wound healing. Current research suggests that nitric oxide and several nitric oxide donors can exert biologic effects, although the particular net responses of cells contributing to wound repair are context-dependent.

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Section: Wound and Tissue Responses To Nitric Oxidementioning

confidence: 85%

Nitric oxide in wound-healing

et al. 2005

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“…In several studies on colon anastomosis, bone fracture, and cutaneous wound healing, the reparative role of NO through upregulation of iNOS has been well demonstrated (10,50,51). Similarly, KLF6 plays a direct anti-apoptotic role in conditions of acute injury.…”

Section: Fig 7 Nacn Exposure Up-regulates Klf6 and Inos Mrnas And Pmentioning

confidence: 99%

Transcriptional Activation of the Human Inducible Nitric-oxide Synthase Promoter by Krüppel-like Factor 6

Warke

Nambiar

Krishnan

et al. 2003

Journal of Biological Chemistry

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Nitric oxide is a ubiquitous free radical that plays a key role in a broad spectrum of signaling pathways in physiological and pathophysiological processes. We have explored the transcriptional regulation of inducible nitric-oxide synthase (iNOS) by Krü ppel-like factor 6 (KLF6), an Sp1-like zinc finger transcription factor. Study of serial deletion constructs of the iNOS promoter revealed that the proximal 0.63-kb region can support a 3-6-fold reporter activity similar to that of the fulllength 16-kb promoter. Within the 0.63-kb region, we identified two CACCC sites (؊164 to ؊168 and ؊261 to ؊265) that bound KLF6 in both electrophoretic mobility shift and chromatin immunoprecipitation assays. Mutation of both these sites abrogated the KLF6-induced enhancement of the 0.63-kb iNOS promoter activity. The binding of KLF6 to the iNOS promoter was significantly increased in Jurkat cells, primary T lymphocytes, and COS-7 cells subjected to NaCN-induced hypoxia, heat shock, serum starvation, and phorbol 12-myristate 13-acetate/A23187 ionophore stimulation. Furthermore, in KLF6-transfected and NaCN-treated COS-7 cells, there was a 3-4-fold increase in the expression of the endogenous iNOS mRNA and protein that correlated with increased production of nitric oxide. These findings indicate that KLF6 is a potential transactivator of the human iNOS promoter in diverse pathophysiological conditions. Nitric-oxide synthases are key proteins that produce NO and thereby regulate many important biological processes. NO is generated during the oxidation of L-arginine to L-citrulline by at least three different isoforms of nitric-oxide synthase. Endothelial and neuronal nitric-oxide synthases are constitutively expressed, and their activity is Ca 2ϩ -and calmodulin-dependent, whereas the third isoform is transcriptionally inducible (iNOS), 1 and its activity is independent of Ca 2ϩ and calmodulin and can produce very high levels of nitric oxide over a sustained period of time (1, 2). It has been shown that iNOS is transcriptionally up-regulated in pathophysiologic conditions such as hypoxia, ischemia-reperfusion injury, and trauma and by reactive oxygen species (3, 4).

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“…All 3 NOS isoforms are expressed in skin [34 -37]. NO levels are elevated in normal burn wounds [38,39] and mice with targeted deletion of each of NOS genes display delayed cutaneous wound healing [40 -42].…”

Section: Introductionmentioning

confidence: 99%

Substance P Enhances Wound Closure in Nitric Oxide Synthase Knockout Mice

Muangman

Tamura

Muffley

et al. 2009

Journal of Surgical Research

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Introduction. The neuropeptide, substance P (SP), up-regulates nitric oxide production (NO). The purpose of this study was to determine whether SP enhances response to cutaneous injury in nitric oxide synthase knockout (NOS null) mice.Methods. We studied mice with targeted deletions of the 3 NOS genes, neuronal NOS, inducible NOS, or endothelial NOS. Full thickness dorsal wounds were treated daily (d 0 -6) with topical SP or normal saline (NaCl). Wounds were analyzed by flow cytometry for macrophage, leukocyte, endothelial, and dendritic cells. Healing time and wound epithelialization were compared using analysis of variance.Results. Wound closure in the 3 NOS null mice was slower than the control mice (P < 0.05). SP treatment enhanced wound closure in NOS null mice (P < 0.02). NOS null wounds exhibited reduced inflammation. SP increased macrophage, leukocyte, and dendritic cell densities at d 3 and d 7 (P < 0.05) in all NOS null mice. SP increased endothelial cell number in neuronal NOS and inducible NOS null mice, but not in endothelial NOS null mice (P > 0.05).Conclusions. SP ameliorated the impaired wound healing response observed in NOS null mice by enhancing wound closure kinetics and epithelialization. SP increased inflammatory cell density in the wounds supporting the essential role of inflammatory cells, especially macrophages, in wound repair.

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Expression of inducible nitric oxide synthase in human burn wounds

Cited by 47 publications

References 8 publications

Nitric oxide in wound-healing

Nitric oxide in wound-healing

Transcriptional Activation of the Human Inducible Nitric-oxide Synthase Promoter by Krüppel-like Factor 6

Substance P Enhances Wound Closure in Nitric Oxide Synthase Knockout Mice

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