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 @entity19 astrocytes. Here, we extend these studies to assess the immunogenic role of both mitochondrial DNA and RNA isolated from @entity273 (HP) treated HA1 cells (designated "DeMPs" for degraded mitochondrial polynucleotides) using @entity19 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 ( @entity777 , @entity8929 , and @entity637 ) and Type I interferon ( @entity12419 and @entity12421 ). Cont mtDNA induced @entity777 and @entity8929 production, and this effect was even greater with @entity69247 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 @entity69247 DNA, @entity69247 RNA attenuated rather than potentiated the cont mtRNA cytokine inductions. This attenuation effect was not accompanied by an @entity1618 or @entity641 anti-inflammatory response. All @entity69247 effects were observed at multiple oxidant concentrations. Finally, @entity69247 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.

Oxidized and Original article degraded mitochondrial polynucleotides (DeMPs), especially RNA, are potent immunogenic regulators in primary XXXX macrophages.

@entity8929 :: ('17224(Tax:10090)', 'Gene') :: ['MCP-1'] @entity69247 :: ('MESH:C104301', 'Chemical') :: ['DeMP'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity641 :: ('21803(Tax:10090)', 'Gene') :: ['TGFb'] @entity12421 :: ('15977(Tax:10090)', 'Gene') :: ['IFN-b'] @entity1618 :: ('16153(Tax:10090)', 'Gene') :: ['IL-10'] @entity273 :: ('MESH:D006861', 'Chemical') :: ['hydrogen peroxide'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['IL-6'] @entity12419 :: ('111654(Tax:10090)', 'Gene') :: ['IFN-a'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['TNFa']
@entity19 :: (10090,Species) :: ['mouse']
