Related Experiment Video
Updated: May 24, 2026
Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
Published on: April 6, 2022
Ultraviolet B induces high mobility group box 1 release from mouse peritoneal macrophages in vitro via caspase-1
Rituparna Chakraborty1, Kunal H Bhatt, Ajit Sodhi
1School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.
Abstract:
High mobility group box 1 (HMGB1) protein is a unique non histone nuclear protein that acts extracellularly as a mediator of delayed inflammation. Sub lethal dose of UVB triggers the release of cytokines from macrophages (MΦs). Adding to the panoply of UVB induced cytokines; it is reported that UVB induces HMGB1 release from mouse peritoneal MΦs in time and partially dose dependent manner, independent of TNF-α. UVB also enhanced the transcription of HMGB1 gene and expression of cellular protein, which influences its subsequent release. HMGB1 is secreted by an unconventional secretion pathway of unknown mechanism. Caspase-1 has been shown to function as a general regulator of stress induced unconventional secretion for a number of cytokines. In the present study, we have observed that pharmacological inhibitors specific for caspase-1 (ZVAD and YVAD) abrogated UVB induced HMGB1 release from MΦs. This effect was most likely mediated via physical interaction between HMGB1 and active caspase-1 (p10 and p20) as demonstrated by immunoprecipitation. In addition, it was found that HMGB1 and active caspase-1 p20 release depends on UVB mediated enhancement of intracellular Ca(2+). Thus our data suggests that optimal dose of UVB (50 mJ/cm(2)) induces HMGB1 upregulation and active release from mouse peritoneal MΦs which is mediated by caspase-1 in a Ca(2+) dependent manner.
Insights
Ultraviolet B (UVB) radiation triggers the release of High mobility group box 1 (HMGB1) from macrophages. This release is mediated by caspase-1 in a calcium-dependent manner.
Area of Science:
- Immunology
- Molecular Biology
- Dermatology
Background:
- High mobility group box 1 (HMGB1) is a nuclear protein that mediates delayed inflammation extracellularly.
- Sub-lethal doses of ultraviolet B (UVB) radiation induce cytokine release from macrophages (MΦs).
- UVB radiation induces HMGB1 release from mouse peritoneal MΦs, independent of TNF-α, and enhances HMGB1 gene transcription and protein expression.
Purpose of the Study:
- To investigate the mechanism of UVB-induced HMGB1 release from MΦs.
- To determine the role of caspase-1 in this process.
- To explore the involvement of intracellular calcium (Ca2+) in UVB-induced HMGB1 release.
Main Methods:
- Utilized pharmacological inhibitors specific for caspase-1 (ZVAD and YVAD).
- Employed immunoprecipitation to demonstrate physical interaction between HMGB1 and active caspase-1.
- Measured intracellular Ca2+ levels following UVB exposure.
Main Results:
- Caspase-1 inhibitors abrogated UVB-induced HMGB1 release from MΦs.
- Physical interaction was observed between HMGB1 and active caspase-1 (p10 and p20 subunits).
- Both HMGB1 and active caspase-1 p20 release were dependent on UVB-enhanced intracellular Ca2+.
Conclusions:
- UVB radiation induces HMGB1 upregulation and active release from mouse peritoneal MΦs.
- This release is mediated by caspase-1 in a Ca2+-dependent pathway.
- Caspase-1 acts as a regulator of UVB-induced unconventional secretion of HMGB1.
