Ultraviolet Light (UVB and UVA) Induces the Damage-Responsive Transcription Factor CHOP/gadd153 in Murine and Human Epidermis: Evidence for a Mechanism Specific to Intact Skin

Abstract

C/EBP-homologous protein (CHOP)/gadd153 (or CHOP) is a transcription factor induced by endoplasmic reticulum (ER) stress. Forcible overexpression of CHOP causes apoptosis in keratinocytes in culture. Here, we asked whether CHOP might be increased in the skin after UVB (280-320 nm) exposure, thus implicating CHOP in sunburn cell (SBC) formation. SKH-1 hairless mice were exposed to a ultraviolet (UV) source (80 mJ per cm2; approximately 74% UVB, approximately 16% UVA), and skin biopsies examined by immunohistology and immunoprecipitation. Compared with non-irradiated epidermis, CHOP expression was significantly increased at 30 min, and reached maximal levels by 24 h. Similar increases in CHOP following UVB exposure were observed in human buttock skin. The time course of CHOP expression preceded SBC formation and another marker of apoptosis, caspase-3 cleavage. Intracellular CHOP accumulated mainly in cytoplasmic and perinuclear locations, with little remaining in the nucleus. To examine mechanisms, cultured keratinocytes were irradiated in vitro and examined by western blotting. Under conditions that eliminated ER stress because of cell handling, CHOP did not accumulate (and was in fact decreased) in the cells. Thus, induction of CHOP in keratinocytes requires factors present only in the native skin. Overall, the data suggest that CHOP participates in adaptive responses of the epidermis following UVB/UVA exposure in vivo.

Ultraviolet A Induces Endoplasmic Reticulum Stress Response in Human Dermal Fibroblasts

“…Previously, Kaufman and colleagues reported that UVC (254 nm) activates the PERK pathway in COS-1, MCF-7 and HIT cells (Wu et al, 2002), and Maytin and colleagues showed that UV light consisting of 74% UVB (280-320 nm) and 16% UVA induced the transcription of CHOP in murine epidermis (Anand et al, 2005). Recently, Kanekura and colleagues revealed that UVB (around 302 nm) activated the ATF6 and IRE1 pathways, but not the PERK pathway in human keratinocytes (Mera et al, 2010); however, to the authors' knowledge, this is the first report demonstrating that UVA (315-400 nm) activates the ER stress response in eukaryotic cells.…”

Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

“…UVA, UVB, and UVC are all capable of stimulating ROS production 73 as well as overlapping stress response pathways 74 including ER stress. 75 Which particular subtle difference distinguishes between ICD and non-ICD is an avenue worth investigating.…”

Regulation of Cathelicidin Antimicrobial Peptide Expression by an Endoplasmic Reticulum (ER) Stress Signaling, Vitamin D Receptor-independent Pathway

“…UV irradiation (17,19), oxidative stress, and wound injury (20), also initiate ER stress responses including downstream activation of the transcription factor, NF-B (16). Because several stressors also up-regulate CAMP expression and because ER stress/activation ubiquitously occurs in mammalian cells, we hypothesized here that ER stress-mediated signals could stimulate CAMP expression in epithelial cells exposed to external perturbations, thereby restoring or enhancing antimicrobial defense barrier(s).…”