ArticleWound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society2020
Anti-inflammatory effects of haptoglobin on LPS-stimulated macrophages: Role of HMGB1 signaling and implications in chronic wound healing.
Article in Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
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- A mendelian randomization analysis of the associations between haptoglobin and multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Helminth protein enhances wound healing by inhibiting fibrosis and promoting tissue regeneration.Life science alliance · 2024Article
- Effective protective mechanisms of HO-1 in diabetic complications: a narrative review.Cell death discovery · 2024Review
- A bioelectronic device for electric field treatment of wounds reduces inflammation in an in vivo mouse model.PloS one · 2024Article
- Advances in stem cell therapy for diabetic foot.Frontiers in genetics · 2024Review
- A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis.Frontiers in microbiology · 2023Review
- Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight.Frontiers in bioengineering and biotechnology · 2023Review
- Maturation of the medaka immune system depends on reciprocal interactions between the microbiota and the intestinal tract.Frontiers in immunology · 2023Article
- Cellular Immune Signal Exchange From Ischemic Stroke to Intestinal Lesions Through Brain-Gut Axis.Frontiers in immunology · 2022Review
- Progress on haptoglobin and metabolic diseases.World journal of diabetes · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Nonhealing wounds possess elevated numbers of pro-inflammatory M1 macrophages, which fail to transition to anti-inflammatory M2 phenotypes that promote healing. Hemoglobin (Hb) and haptoglobin (Hp) proteins, when complexed (Hb-Hp), can elicit M2-like macrophages through the heme oxygenase-1 (HO-1) pathway. Despite the fact that nonhealing wounds are chronically inflamed, previous studies have focused on non-inflammatory systems, and do not thoroughly compare the effects of complexed vs individual proteins. We aimed to investigate the effect of Hb/Hp treatments on macrophage phenotype in an inflammatory, lipopolysaccharide (LPS)-stimulated environment, similar to chronic wounds. Human M1 macrophages were cultured in vitro and stimulated with LPS. Concurrently, Hp, Hb, or Hb-Hp complexes were delivered. The next day, 27 proteins related to inflammation were measured in the supernatants. Hp treatment decreased a majority of inflammatory factors, Hb increased many, and Hb-Hp had intermediate trends, indicating that Hp attenuated overall inflammation to the greatest extent. From this data, Ingenuity Pathway Analysis software identified high motility group box 1 (HMGB1) as a key canonical pathway-strongly down-regulated from Hp, strongly up-regulated from Hb, and slightly activated from Hb-Hp. HMGB1 measurements in macrophage supernatants confirmed this trend. In vivo results in diabetic mice with biopsy punch wounds demonstrated accelerated wound closure with Hp treatment, and delayed wound closure with Hb treatment. This work specifically studied Hb/Hp effects on macrophages in a highly inflammatory environment relevant to chronic wound healing. Results show that Hp-and not Hb-Hp, which is known to be superior in noninflammatory conditions-reduces inflammation in LPS-stimulated macrophages, and HMGB1 signaling is also implicated. Overall, Hp treatment on M1 macrophages in vitro reduced the inflammatory secretion profile, and also exhibited benefits in in silico and in vivo wound-healing models.
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Registered trials
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