Comparison of stress-induced PRINS gene expression in normal human keratinocytes and HaCaT cells

Abstract

Psoriasis is a chronic inflammatory skin disease that affects approximately 2-4% of the population. We recently described a novel non-coding RNA, psoriasis susceptibility related RNA gene induced by stress (PRINS), that was overexpressed in non-lesional psoriatic epidermis, and its expression was induced by various stress factors such as serum starvation, contact inhibition, ultraviolet (UV)-B irradiation, viral infection and translational inhibition in HaCaT cells. In the present work we set out to compare the stress and microbial agent-induced PRINS expression in normal human keratinocytes (NHKs) and HaCaT cells. Since nuclear factor-κB (NF-κB) is involved in the cellular stress response, we sought to explore whether there is a connection between the NF-κB and PRINS-mediated signal transduction pathways in NHKs and HaCaT cells. We found that the PRINS expression responded differentially to various stress signals and microbial agents in HaCaT cells and in NHKs: after translational inhibition and UV-B treatment, similar induction of PRINS expression occurred with different time courses while after microbial agent treatment, the PRINS expression was significantly induced in HaCaT cells, whereas we could not detect similar changes in NHKs. To explore whether the known NF-κB abnormalities in HaCaT cells could be related to this differential PRINS expression, we silenced the PRINS gene expression with small interfering RNA (siRNA) in both HaCaT cells and in NHKs and monitored NF-κB signal transduction after lipopolysaccharide (LPS) treatment. Silencing of PRINS had no effect on LPS-induced NF-κB activity either in HaCaT cells or in NHKs. Our results indicate that PRINS probably affects keratinocytes functions independently of NF-κB signalling.

Long Noncoding RNAs in HPV-Induced Oncogenesis

“…145 PRINS expression is increased under stress environment, such as viral infection (herpes simplex virus), ultraviolet B irradiation, and translational inhibition, while it was showed to be regulated by the proliferation and differentiation state of keratinocytes. 145 Although nuclear factor kappa B (NF-κB) is involved in the cellular stress response, PRINS works independently of this pathway 146 and may mediate nucleophosmin response in the skin in stress conditions. 147 PRINS showed to positively regulate G1P3, an interferon-inducible gene with antiapoptotic effects in cancer cells and, at least in patients with psoriasis, it can contribute to a decreased sensitivity to spontaneous keratinocyte apoptosis.…”

Investigations on molecular mechanisms of epithelial cell stress responses

“…It is well documented that distinct differences exist between the responses of NHKs and HaCaT cells to UV-B irradiation and HaCaT cells are known to be more sensitive to UV-B-induced apoptosis [174]. However, the most striking differences we saw between the two cell types in PRINS expression were after incubation with microbial compounds: while PRINS expression in HaCaT cells was highly elevated in response to all of applied microbial agents, a significant elevation of PRINS expression in NHKs was observed only after incubation with LPS, but none of the other microbial agents [38].…”

“…HaCaT cells, in NHKs the same stressors either induced PRINS with a differential pattern (translation inhibition with cycloheximide and UV-B irradiation) or did not induce PRINS expression (microbial compounds) [38]. These data indicate a differential role for PRINS in the cellular stress response in NHKs and in the immortalized HaCaT cells.…”

“…These data led us to hypothesize that PRINS is essential for the survival of keratinocytes under stress conditions. in NHKs, respectively [38]. It is well documented that distinct differences exist between the responses of NHKs and HaCaT cells to UV-B irradiation and HaCaT cells are known to be more sensitive to UV-B-induced apoptosis [174].…”

Role of IRF6 in epithelial cell-mediated host defence and inflammation

“…Primary keratinocytes and HaCaT cells also respond differently to various stress signals and microbial agents (Bari, Bacsa et al 2011). Ultraviolet (UV) radiation induced stress caused robust upregulation of TNF-α production in primary keratinocytes, while it was very mildly produced by…”