PMID- 32040528
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 15
IP  - 2
DP  - 2020
TI  - 1,25-hydroxyvitamin D3 decreases endoplasmic reticulum stress-induced 
      inflammatory response in mammary epithelial cells.
PG  - e0228945
LID - 10.1371/journal.pone.0228945 [doi]
LID - e0228945
AB  - Recent studies indicated that intramammary administration of active vitamin D3 
      hormone (1,25D3) inhibits the inflammatory process associated with mastitis. We 
      hypothesized that attenuation of endoplasmic reticulum (ER) stress by 1,25D3 in 
      mammary epithelial cells (MECs) is an important cellular mechanism contributing 
      to this beneficial effect of intramammary treatment with 1,25D3. To test this 
      hypothesis, the effect of 1,25D3 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 1,25D3 (100 nM) inhibited TG (10 nM)- and TM (1 mug/mL)-induced 
      mRNA and/or protein levels of ATF4, ATF6, DDIT3 and HSPA5 in MCF-7 cells (P < 
      0.05). In addition, 1,25D3 (100 nM) antagonized the effect of TG (10 nM) and TM 
      (1 mug/mL) on mRNA and protein levels of VDR and mRNA levels of genes involved in 
      production and degradation of 1,25D3 in MCF-7 cells (P < 0.05). Moreover, 1,25D3 
      (100 nM) inhibited nuclear factor-kappaB (NF-kappaB) activation in response to TM (10 nM) 
      and TG (1 mug/mL) in MCF-7 cells. In conclusion, the present findings show that 
      1,25D3 is effective in attenuating ER stress and the NF-kappaB-driven inflammatory 
      response in MCF-7 cells. This indicates that attenuation of ER stress by 1,25D3 
      in MECs may contribute to the recently observed inhibitory effect of intramammary 
      treatment of dairy cows with 1,25D3 on the inflammatory process associated with 
      mastitis.
FAU - Wen, Gaiping
AU  - Wen G
AD  - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University 
      Giessen, Giessen, Germany.
FAU - Eder, Klaus
AU  - Eder K
AD  - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University 
      Giessen, Giessen, Germany.
FAU - Ringseis, Robert
AU  - Ringseis R
AUID- ORCID: 0000-0002-1321-4820
AD  - Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University 
      Giessen, Giessen, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200210
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (VDR protein, human)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Breast/*drug effects/*metabolism/pathology
MH  - Calcitriol/metabolism/*pharmacology
MH  - Cattle
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Epithelial Cells/drug effects/metabolism/pathology
MH  - Female
MH  - Humans
MH  - Inflammation/drug therapy/metabolism/pathology
MH  - MCF-7 Cells
MH  - Mastitis/drug therapy/metabolism/pathology
MH  - Mastitis, Bovine/drug therapy/metabolism/pathology
MH  - NF-kappa B/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Calcitriol/genetics/metabolism
MH  - Thapsigargin/toxicity
MH  - Tunicamycin/toxicity
PMC - PMC7010291
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/02/11 06:00
MHDA- 2020/05/12 06:00
PMCR- 2020/02/10
CRDT- 2020/02/11 06:00
PHST- 2019/09/10 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/02/11 06:00 [entrez]
PHST- 2020/02/11 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2020/02/10 00:00 [pmc-release]
AID - PONE-D-19-25448 [pii]
AID - 10.1371/journal.pone.0228945 [doi]
PST - epublish
SO  - PLoS One. 2020 Feb 10;15(2):e0228945. doi: 10.1371/journal.pone.0228945. 
      eCollection 2020.