PMID- 28179110
OWN - NLM
STAT- MEDLINE
DCOM- 20171214
LR  - 20191210
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 104
DP  - 2017 Mar
TI  - Oxidized and Original article degraded mitochondrial polynucleotides (DeMPs), 
      especially RNA, are potent immunogenic regulators in primary mouse macrophages.
PG  - 371-379
LID - S0891-5849(17)30069-2 [pii]
LID - 10.1016/j.freeradbiomed.2017.02.009 [doi]
AB  - Certain mitochondrial components can act as damage-associated molecular patterns 
      (DAMPs) or danger signals, triggering a proinflammatory response in target 
      (usually immune) cells. We previously reported the selective degradation of 
      mitochondrial DNA and RNA in response to cellular oxidative stress, and the 
      immunogenic effect of this DNA in primary mouse astrocytes. Here, we extend these 
      studies to assess the immunogenic role of both mitochondrial DNA and RNA isolated 
      from hydrogen peroxide (HP) treated HA1 cells (designated "DeMPs" for degraded 
      mitochondrial polynucleotides) using mouse bone marrow derived macrophages 
      (BMDMs), a conventional immune cell type. DeMPs and control mitochondrial DNA 
      (cont mtDNA) and RNA (cont mtRNA) were transfected into BMDMs and cell-free media 
      analyzed for the presence of proinflammatory cytokines (IL-6, MCP-1, and TNFalpha) 
      and Type I interferon (IFN-alpha and IFN-beta). Cont mtDNA induced IL-6 and MCP-1 
      production, and this effect was even greater with DeMP DNA. A similar response 
      was observed for Type I interferons. An even stronger induction of 
      proinflammatory cytokine and type 1 interferons was observed for cont mtRNA. 
      However, contrary to DeMP DNA, DeMP RNA attenuated rather than potentiated the 
      cont mtRNA cytokine inductions. This attenuation effect was not accompanied by an 
      IL-10 or TGFbeta anti-inflammatory response. All DeMP effects were observed at 
      multiple oxidant concentrations. Finally, DeMP production and immunogenicity 
      overlaps with cellular adaptive response and so may contribute to cellular 
      oxidant protection. These results provide new insight into the immunogenicity of 
      mitochondrial polynucleotides, and identify new roles and selective consequences 
      of cellular oxidation.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Saxena, Abhinav R
AU  - Saxena AR
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA; St. George's University School of Medicine, Grenada, West Indies.
FAU - Gao, Linda Y
AU  - Gao LY
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA.
FAU - Srivatsa, Shachi
AU  - Srivatsa S
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA.
FAU - Bobersky, Elizabeth Z
AU  - Bobersky EZ
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA.
FAU - Periasamy, Sivakumar
AU  - Periasamy S
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA.
FAU - Hunt, Danielle T
AU  - Hunt DT
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA.
FAU - Altman, Kyle E
AU  - Altman KE
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA.
FAU - Crawford, Dana R
AU  - Crawford DR
AD  - Department of Immunology and Microbial Disease, Albany Medical College, Albany, 
      NY 12208, USA. Electronic address: crawfod@mail.amc.edu.
LA  - eng
PT  - Journal Article
DEP - 20170204
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Cytokines)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (RNA, Mitochondrial)
RN  - 63231-63-0 (RNA)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Cytokines/biosynthesis
MH  - DNA, Mitochondrial/drug effects/genetics/metabolism
MH  - Hydrogen Peroxide/toxicity
MH  - Macrophages/drug effects/*metabolism/pathology
MH  - Mice
MH  - Mitochondria/*drug effects/metabolism/pathology
MH  - Mitophagy/drug effects/genetics
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*drug effects/genetics
MH  - RNA/*genetics/metabolism
MH  - RNA Stability/drug effects/genetics
MH  - RNA, Mitochondrial
OTO - NOTNLM
OT  - DAMPs
OT  - DeMPs
OT  - Degraded mitochondrial polynucleotides
OT  - Hydrogen peroxide
OT  - Macrophages
OT  - Mitochondria
OT  - Oxidative stress
OT  - Proinflammatory cytokine
EDAT- 2017/02/10 06:00
MHDA- 2017/12/15 06:00
CRDT- 2017/02/10 06:00
PHST- 2017/01/04 00:00 [received]
PHST- 2017/01/26 00:00 [revised]
PHST- 2017/02/04 00:00 [accepted]
PHST- 2017/02/10 06:00 [pubmed]
PHST- 2017/12/15 06:00 [medline]
PHST- 2017/02/10 06:00 [entrez]
AID - S0891-5849(17)30069-2 [pii]
AID - 10.1016/j.freeradbiomed.2017.02.009 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2017 Mar;104:371-379. doi: 
      10.1016/j.freeradbiomed.2017.02.009. Epub 2017 Feb 4.