Macrophage-Derived Heme-Oxygenase-1: Expression, Regulation, and Possible Functions in Skin Repair

Kämpfer, Heiko; Kolb, Nicole; Manderscheid, Markus; Wetzler, Christian; Pfeilschifter, Josef; Frank, Stefan

doi:10.1007/bf03401854

Cited by 31 publications

(31 citation statements)

References 63 publications

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“…We therefore suspected that the HO-1 in this study was derived from macrophages. This result is consistent with a report on the skin wound repair process in mice [40], and also with a previous report on HO expression in macrophages [34].…”

Section: Discussionsupporting

confidence: 95%

Time-course changes in the expression of heme oxygenase-1 in human subcutaneous hemorrhage

Nakajima

Hayakawa

Yajima

et al. 2006

Forensic Science International

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Section: Discussionsupporting

confidence: 95%

Time-course changes in the expression of heme oxygenase-1 in human subcutaneous hemorrhage

Nakajima

Hayakawa

Yajima

et al. 2006

Forensic Science International

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“…In excisional wounds and psoriatic skin, HMOX1 mRNA, and protein were observed to be increased in the hyperproliferative epidermis and infiltrating macrophages [30,32,33]. Moreover, various models of inflammation have demonstrated that pharmacological modulation of HMOX1 expression can have a positive impact on the cutaneous wound healing process.…”

Section: Discussionmentioning

confidence: 95%

An assessment of transcriptional changes in porcine skin exposed to bromine vapor

Rogers

Price

Wendling

et al. 2011

J Biochem & Molecular Tox

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Bromine is an industrial chemical that can cause severe cutaneous burns. This study was a preliminary investigation into the effect of cutaneous exposure to bromine vapor using a weanling swine burn model and microarray analysis. Ventral abdominal sites were exposed to a mean calculated bromine vapor concentration of 0.69 g L(-1) for 10 or 20 min. At 48 h postexposure, total RNA from skin samples was isolated, processed, and hybridized to Affymetrix GeneChip Porcine Genome Arrays. Expression analysis revealed that bromine vapor exposure for 10 or 20 min promoted similar transcriptional changes in the number of significantly modulated probe sets. A minimum of 83% of the probe sets was similar for both exposure times. Ingenuity pathways analysis revealed eight common biological functions among the top 10 functions of each experimental group, in which 30 genes were commonly shared among 19 significantly altered signaling pathways. Transcripts encoding heme oxygenase 1, interleukin-1β, interleukin 2 receptor gamma chain, and plasminogen activator inhibitor-1 were identified as common potential therapeutic targets for Phase II/III clinical trial or FDA-approved drugs. The present study is an initial assessment of the transcriptional responses to cutaneous bromine vapor exposure identifying molecular networks and genes that could serve as targets for developing therapeutics for bromine-induced skin injury.

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“…Thus, by infiltrating, these cells import the HO system into the wounded area and cause protection via the immediate generation of the antiinflammatory and antioxidative heme metabolites biliverdin/ bilirubin and CO, and the up-regulation of ferritin. 50 When HO activity is inhibited by pharmacologic agents such as SnMP, administration of heme aggravated influx of granulocytes and macrophages as compared with heme treatment alone. HO activity may, via the generation of antioxidants biliverdin/bilirubin and vasodilator CO, function as a feedback mechanism by downregulating adhesion molecules and thereby alleviating recruitment of immune cells and the immune response.…”

Section: Discussionmentioning

confidence: 99%

“…HO-1 is present mainly near the basal membrane in proliferating keratinocytes. 50 HO-2, the HO isoform that is able to bind heme, may therefore function as a first scavenger against heme-induced insults, whereas HO-1, present in the first layers of the epidermis and in infiltrating leukocytes, degrades heme to generate its potent cytoprotective breakdown products. Therefore, HO seems to form a general protective layer to withstand the continuous oxidative and mechanical insults of which the skin daily suffers.…”

Section: Discussionmentioning

confidence: 99%

The heme-heme oxygenase system: a molecular switch in wound healing

Wagener

Beurden

Hoff

et al. 2003

Blood

118

128

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When cells are injured they release their contents, resulting in a local accumulation of free heme proteins and heme. Here, we investigated the involvement of heme and its degrading enzyme heme oxygenase (HO) in the inflammatory process during wound healing. We observed that heme directly accumulates at the edges of the wound after inflicting a wound in the palate of Wistar rats. This coincided with an increased adhesion molecule expression and the recruitment of leukocytes. To prove that heme is responsible for the recruitment of leukocytes, heme was administered intradermally 24 hours prior to injury. A clear heme-induced influx of both macrophages and granulocytes was observed. When examining the HO isoforms, HO-1 and HO-2, we found that HO-2 was present in the entire submucosa. Surprisingly, we observed also that HO-1 is significantly expressed in the epithelium of both the mucosa and the skin of animals without wounds. On inflammation, HO-1 expression increased, particularly in infiltrating cells during the resolution phase of inflammation. Interestingly, we observed that heme-induced influx of leukocytes was highly elevated after pharmacologic inhibition of HO activity. These observations suggest that the heme-HO system is closely involved in the control of wound healing. Our results demonstrate that the local release of heme may be a physiologic trigger to start inflammatory processes, whereas HO-1 antagonizes inflammation by attenuating adhesive interactions and cellular infiltration. Moreover, the basal level of HO expression in the skin may serve as a first protective environment against acute oxidative and inflammatory insults. (Blood. 2003;102: 521-528)

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Macrophage-Derived Heme-Oxygenase-1: Expression, Regulation, and Possible Functions in Skin Repair

Cited by 31 publications

References 63 publications

Time-course changes in the expression of heme oxygenase-1 in human subcutaneous hemorrhage

Time-course changes in the expression of heme oxygenase-1 in human subcutaneous hemorrhage

An assessment of transcriptional changes in porcine skin exposed to bromine vapor

The heme-heme oxygenase system: a molecular switch in wound healing

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