Journal article

Authors list: Wen, Gaiping; Eder, Klaus; Ringseis, Robert

Publication year: 2020

Journal: PLoS ONE

Volume number: 15

Issue number: 2

ISSN: 1932-6203

Open access status: Gold

DOI Link: https://doi.org/10.1371/journal.pone.0228945

Publisher: Public Library of Science

Abstract: 
Recent studies indicated that intramammary administration of active vitamin D-3 hormone (1,25D(3)) inhibits the inflammatory process associated with mastitis. We hypothesized that attenuation of endoplasmic reticulum (ER) stress by 1,25D(3) in mammary epithelial cells (MECs) is an important cellular mechanism contributing to this beneficial effect of intramammary treatment with 1,25D(3). To test this hypothesis, the effect of 1,25D(3) was studied on induction of ER stress in a transformed human MEC line, MCF-7 cells. Treatment with two different ER stress inducers, thapsigargin (TG) and tunicamycin (TM), caused a dose-dependent induction of ER stress as evident from up-regulation of protein kinase RNA-like ER kinase (PERK), heat shock protein family A (Hsp70) member 5 (HSPA5), activating transcription factor (ATF4), ATF6, DNA damage inducible transcript 3 (DDIT3) and spliced X-box binding protein 1 (sXBP1) and impaired cell viability and decreased expression of vitamin D receptor (VDR) in MCF-7 cells (P < 0.05). Treatment with 1,25D(3) (100 nM) inhibited TG (10 nM)-and TM (1 mu g/mL)-induced mRNA and/or protein levels of ATF4, ATF6, DDIT3 and HSPA5 in MCF-7 cells (P < 0.05). In addition, 1,25D(3) (100 nM) antagonized the effect of TG (10 nM) and TM (1 mu g/mL) on mRNA and protein levels of VDR and mRNA levels of genes involved in production and degradation of 1,25D(3) in MCF-7 cells (P < 0.05). Moreover, 1,25D(3) (100 nM) inhibited nuclear factor-kappa B (NF-kappa B) activation in response to TM (10 nM) and TG (1 mu g/mL) in MCF-7 cells. In conclusion, the present findings show that 1,25D(3) is effective in attenuating ER stress and the NF-kappa B-driven inflammatory response in MCF-7 cells. This indicates that attenuation of ER stress by 1,25D(3) in MECs may contribute to the recently observed inhibitory effect of intramammary treatment of dairy cows with 1,25D(3) on the inflammatory process associated with mastitis.

Harvard Citation style: Wen, G., Eder, K. and Ringseis, R. (2020) 1,25-hydroxyvitamin D3 decreases endoplasmic reticulum stress-induced inflammatory response in mammary epithelial cells, PLoS ONE, 15(2), Article e0228945. https://doi.org/10.1371/journal.pone.0228945

APA Citation style: Wen, G., Eder, K., & Ringseis, R. (2020). 1,25-hydroxyvitamin D3 decreases endoplasmic reticulum stress-induced inflammatory response in mammary epithelial cells. PLoS ONE. 15(2), Article e0228945. https://doi.org/10.1371/journal.pone.0228945