title: Ultraviolet B induces high mobility group box 1 release from mouse peritoneal macrophages in vitro via caspase-1 mediated secretion pathway.
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.
authors.affiliation: School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Kunal H
authors.initials: KH
authors.lastname: Bhatt
authors.forename: Ajit
authors.initials: A
authors.lastname: Sodhi
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000528:radiation effects; D020170:Caspase 1 / Q000378:metabolism*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology; D055571:Secretory Pathway / Q000187:drug effects / Q000528:radiation effects; D015533:Transcriptional Activation / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D009842:Oligopeptides; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; D025741:HMGA1a Protein; D020170:Caspase 1