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Updated: Feb 3, 2026

A High Yield and Cost-efficient Expression System of Human Granzymes in Mammalian Cells
Published on: June 10, 2015
Granzyme K Expressed by Classically Activated Macrophages Contributes to Inflammation and Impaired Remodeling
Christopher T Turner1, Matthew R Zeglinski1, Katlyn C Richardson1
1International Collaboration On Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Granzyme K (GzmK), traditionally described as a pro-apoptotic, granule-secreted serine protease, has been proposed to promote inflammation. Found at low levels in the plasma of healthy individuals, GzmK is markedly elevated in response to sepsis and infection. In this study we investigated the role of GzmK in inflammation and remodeling in response to thermal injury. In human burn tissue, GzmK was elevated compared with normal skin, with expression predominantly found in macrophages. GzmK was expressed and secreted by cultured human classically activated macrophages. To assess the role of GzmK in response to skin wounding, wild-type or GzmK-/- mice were subjected to grade 2 thermal injury. GzmK-/- mice exhibited improved wound closure, matrix organization, and tensile strength compared with wild-type mice. Reduced proinflammatory IL-6, ICAM-1, VCAM-1, and MCP-1 expressions were observed at 3 days after injury. Additionally, GzmK induced IL-6 expression in keratinocytes and skin fibroblasts that was dependent on PAR-1 activation. Re-epithelialization showed the greatest degree of improvement of all healing parameters, suggesting that keratinocytes are sensitive to GzmK-mediated proteolysis. In support, keratinocytes, but not skin fibroblasts, exposed to GzmK showed impaired wound healing in vitro. In summary, GzmK influences wound healing by augmenting inflammation and impeding epithelialization.
Insights
Granzyme K (GzmK) promotes inflammation and impairs skin healing after burns. Removing GzmK improved wound closure and tissue repair in mice, highlighting its role in thermal injury inflammation.
Area of Science:
- Immunology
- Dermatology
- Protease research
Background:
- Granzyme K (GzmK), a serine protease, is linked to inflammation and elevated in sepsis.
- Its role in thermal injury and wound healing is not well understood.
Purpose of the Study:
- To investigate the role of Granzyme K (GzmK) in inflammation and tissue remodeling following thermal injury.
- To determine GzmK's impact on skin wound healing and epithelialization.
Main Methods:
- Analyzing GzmK expression in human burn tissue and cultured macrophages.
- Utilizing wild-type and GzmK knockout (GzmK-/-) mice subjected to thermal injury.
- Assessing wound closure, matrix organization, tensile strength, and inflammatory markers (IL-6, ICAM-1, VCAM-1, MCP-1).
- Investigating GzmK's effect on keratinocytes and fibroblasts in vitro.
Main Results:
- GzmK was elevated in human burn tissue, primarily in macrophages.
- GzmK knockout mice showed enhanced wound healing, improved matrix organization, and increased tensile strength.
- Reduced levels of key inflammatory markers were observed in GzmK knockout mice.
- GzmK induced IL-6 expression in keratinocytes and fibroblasts, dependent on PAR-1 activation.
- GzmK impaired in vitro keratinocyte wound healing, suggesting sensitivity to its proteolysis.
Conclusions:
- Granzyme K (GzmK) significantly contributes to inflammation and impedes epithelialization during thermal wound healing.
- Targeting GzmK may offer a therapeutic strategy to improve skin wound repair.
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