PMID- 26678450
OWN - NLM
STAT- MEDLINE
DCOM- 20160823
LR  - 20200418
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 30
IP  - 4
DP  - 2016 Apr
TI  - The integrated endoplasmic reticulum stress response in Leishmania amazonensis 
      macrophage infection: the role of X-box binding protein 1 transcription factor.
PG  - 1557-65
LID - 10.1096/fj.15-281550 [doi]
AB  - Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response 
      (IERSR) that ensures cellular survival of ER stress and represents a primordial 
      form of innate immunity. We investigated the role of IERSR duringLeishmania 
      amazonensisinfection. Treatment of RAW 264.7 infected macrophages with the ER 
      stress-inducing agent thapsigargin (TG; 1 muM) increasedL. amazonensisinfectivity 
      in an IFN1-alpha receptor (IFNAR)-dependent manner. In Western blot assays, we showed 
      thatL. amazonensisactivates the inositol-requiring enzyme (IRE1)/ X-box binding 
      protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin 
      immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer 
      and promoter sequences for theIfnbgene by XBP1 in infected RAW 264.7 cells. 
      Knocking down XBP1 expression by transducing RAW 264.7 cells with the short 
      hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation 
      associated with impaired translocation of phosphorylated IFN regulatory 
      transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-beta expression. 
      Knocking down XBP1 expression also increased NO concentration, as determined by 
      Griess reaction and reduced the expression of antioxidant genes, such as heme 
      oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude 
      thatL. amazonensisactivation of XBP1 plays a critical role in infection by 
      protecting the parasites from oxidative stress and increasing IFN1-beta 
      expression.-Dias-Teixeira, K. L., Calegari-Silva, T. C., Dos Santos, G. R. R. M., 
      Vitorino dos Santos, J., Lima, C., Medina, J. M., Aktas, B. H., Lopes, U. G. The 
      integrated endoplasmic reticulum stress response inLeishmania 
      amazonensismacrophage infection: the role of X-box binding protein 1 
      transcription factor.
CI  - (c) FASEB.
FAU - Dias-Teixeira, Karina Luiza
AU  - Dias-Teixeira KL
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Calegari-Silva, Teresa Cristina
AU  - Calegari-Silva TC
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - dos Santos, Guilherme R R M
AU  - dos Santos GR
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Vitorino Dos Santos, Jose
AU  - Vitorino Dos Santos J
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Lima, Carolina
AU  - Lima C
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Medina, Jorge Mansur
AU  - Medina JM
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Aktas, Bertal Huseyin
AU  - Aktas BH
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA.
FAU - Lopes, Ulisses G
AU  - Lopes UG
AD  - *Laboratorio de Parasitologia Molecular, Instituto de Biofisica Carlos Chagas 
      Filho, and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, 
      Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Hematology 
      Laboratory for Translation, Department of Medicine, Brigham and Women's Hospital 
      and Harvard Medical School, Boston, Massachusetts, USA lopesu@biof.ufrj.br.
LA  - eng
PT  - Journal Article
DEP - 20151217
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
RN  - 0 (Xbp1 protein, mouse)
RN  - 67526-95-8 (Thapsigargin)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Endoplasmic Reticulum Stress
MH  - Gene Expression
MH  - HEK293 Cells
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Host-Parasite Interactions
MH  - Humans
MH  - Interferon-beta/genetics/metabolism
MH  - Leishmania/*physiology
MH  - Macrophages/drug effects/*metabolism/*microbiology
MH  - Mice
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA Interference
MH  - Reactive Oxygen Species/metabolism
MH  - Regulatory Factor X Transcription Factors
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thapsigargin/pharmacology
MH  - Transcription Factors/genetics/*metabolism
MH  - X-Box Binding Protein 1
PMC - PMC7163978
OTO - NOTNLM
OT  - ER stress
OT  - IFN1-beta
OT  - XBP1
OT  - oxidative stress
OT  - thapsigargin IRE1
EDAT- 2015/12/19 06:00
MHDA- 2016/08/24 06:00
PMCR- 2020/04/17
CRDT- 2015/12/19 06:00
PHST- 2015/09/28 00:00 [received]
PHST- 2015/12/08 00:00 [accepted]
PHST- 2015/12/19 06:00 [entrez]
PHST- 2015/12/19 06:00 [pubmed]
PHST- 2016/08/24 06:00 [medline]
PHST- 2020/04/17 00:00 [pmc-release]
AID - fj.15-281550 [pii]
AID - FSB2030004018 [pii]
AID - 10.1096/fj.15-281550 [doi]
PST - ppublish
SO  - FASEB J. 2016 Apr;30(4):1557-65. doi: 10.1096/fj.15-281550. Epub 2015 Dec 17.