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Inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains.

Abstract Active participation of endogenous retroviruses (ERVs) in disease processes has been exemplified by the finding that the HERV (human ERV)-W envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We also demonstrated that injury-elicited stressors alter the expression of murine ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to stress (e.g., injury, infection)-elicited systemic glucocorticoid (GC) levels, we examined the GC-stress response of 64 MMTV-MuERV promoters isolated from the genomes of 23 mouse strains. All 64 promoters responded to treatment with a synthetic GC, dexamethasone (DEX), at a wide range from a 0.6- to 85.7-fold increase in reporter activity compared to no treatment. An analysis of the 10 lowest and 10 highest DEX responders revealed specific promoter elements exclusively present in either the three lowest or the two highest responders. Each promoter had a unique profile of transcription regulatory elements and the glucocorticoid response element (GRE) was identified in all promoters with the number of GREs ranging from 2 to 7. The three lowest DEX responders were the only promoters with two GREs. The findings from this study suggest that certain MMTV-MuERVs are more responsive to stress-elicited systemic GC elevation compared to the others. The mouse strain-specific genomic MMTV-MuERV profiles and individual MMTV-MuERVs' differential responses to GC-stress might explain, at least in part, the variable inflammatory responses to injury and/or infection, often observed among different mouse strains.
PMID
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Authors

Mayor MeshTerms
Keywords

Endogenous retrovirus

Glucocorticoid

Glucocorticoid response element

Inflammation

Injury

Mouse mammary tumor virus

Journal Title biochimica et biophysica acta
Publication Year Start




PMID- 27816520
OWN - NLM
STAT- Publisher
DA  - 20161106
LR  - 20161127
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
DP  - 2016 Nov 3
TI  - Inherently variable responses to glucocorticoid stress among endogenous
      retroviruses isolated from 23 mouse strains.
LID - S0925-4439(16)30279-4 [pii]
LID - 10.1016/j.bbadis.2016.10.026 [doi]
AB  - Active participation of endogenous retroviruses (ERVs) in disease processes has
      been exemplified by the finding that the HERV (human ERV)-W envelope protein is
      involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We
      also demonstrated that injury-elicited stressors alter the expression of murine
      ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus
      (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to
      stress (e.g., injury, infection)-elicited systemic glucocorticoid (GC) levels, we
      examined the GC-stress response of 64 MMTV-MuERV promoters isolated from the
      genomes of 23 mouse strains. All 64 promoters responded to treatment with a
      synthetic GC, dexamethasone (DEX), at a wide range from a 0.6- to 85.7-fold
      increase in reporter activity compared to no treatment. An analysis of the 10
      lowest and 10 highest DEX responders revealed specific promoter elements
      exclusively present in either the three lowest or the two highest responders.
      Each promoter had a unique profile of transcription regulatory elements and the
      glucocorticoid response element (GRE) was identified in all promoters with the
      number of GREs ranging from 2 to 7. The three lowest DEX responders were the only
      promoters with two GREs. The findings from this study suggest that certain
      MMTV-MuERVs are more responsive to stress-elicited systemic GC elevation compared
      to the others. The mouse strain-specific genomic MMTV-MuERV profiles and
      individual MMTV-MuERVs' differential responses to GC-stress might explain, at
      least in part, the variable inflammatory responses to injury and/or infection,
      often observed among different mouse strains.
CI  - Copyright A(c) 2016 Elsevier B.V. All rights reserved.
FAU - Hsu, Karen
AU  - Hsu K
AD  - Burn Research, Shriners Hospitals for Children Northern California, Davis,
      Sacramento, CA 95817, USA.
FAU - Lee, Young-Kwan
AU  - Lee YK
AD  - Department of Surgery, University of California, Davis, Sacramento, CA 95817,
      USA.
FAU - Chew, Alex
AU  - Chew A
AD  - Burn Research, Shriners Hospitals for Children Northern California, Davis,
      Sacramento, CA 95817, USA.
FAU - Chiu, Sophia
AU  - Chiu S
AD  - Burn Research, Shriners Hospitals for Children Northern California, Davis,
      Sacramento, CA 95817, USA.
FAU - Lim, Debora
AU  - Lim D
AD  - Department of Surgery, University of California, Davis, Sacramento, CA 95817,
      USA.
FAU - Greenhalgh, David G
AU  - Greenhalgh DG
AD  - Burn Research, Shriners Hospitals for Children Northern California, Davis,
      Sacramento, CA 95817, USA; Department of Surgery, University of California,
      Davis, Sacramento, CA 95817, USA.
FAU - Cho, Kiho
AU  - Cho K
AD  - Burn Research, Shriners Hospitals for Children Northern California, Davis,
      Sacramento, CA 95817, USA; Department of Surgery, University of California,
      Davis, Sacramento, CA 95817, USA. Electronic address: [email protected]
LA  - ENG
PT  - Journal Article
DEP - 20161103
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
OTO - NOTNLM
OT  - Endogenous retrovirus
OT  - Glucocorticoid
OT  - Glucocorticoid response element
OT  - Inflammation
OT  - Injury
OT  - Mouse mammary tumor virus
EDAT- 2016/11/07 06:00
MHDA- 2016/11/07 06:00
CRDT- 2016/11/07 06:00
PHST- 2016/08/01 [received]
PHST- 2016/09/28 [revised]
PHST- 2016/10/27 [accepted]
AID - S0925-4439(16)30279-4 [pii]
AID - 10.1016/j.bbadis.2016.10.026 [doi]
PST - aheadofprint
SO  - Biochim Biophys Acta. 2016 Nov 3. pii: S0925-4439(16)30279-4. doi:
      10.1016/j.bbadis.2016.10.026.

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