Effects of mitochondrial dysfunction on the immunological properties of microglia.
BACKGROUND
Neurodegenerative diseases are characterized by both mitochondrial dysfunction and activation of microglia, the macrophages of the brain. Here, we investigate the effects of mitochondrial dysfunction on the activation profile of microglial cells.


METHODS
We incubated primary mouse microglia with the mitochondrial toxins 3-nitropropionic acid (3-NP) or rotenone. These mitochondrial toxins are known to induce neurodegeneration in humans and in experimental animals. We characterized lipopolysaccharide- (LPS-) induced microglial activation and the alternative, interleukin-4- (IL-4-) induced microglial activation in these mitochondrial toxin-treated microglial cells.


RESULTS
We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta), they did inhibit part of the IL-4-induced alternative activation, as measured by arginase activity and expression, induction of insulin-like growth factor 1 (IGF-1) and the counteraction of the LPS induced cytokine release.


CONCLUSIONS
Mitochondrial dysfunction in microglial cells inhibits part of the IL-4-induced alternative response. Because this alternative activation is considered to be associated with wound healing and an attenuation of inflammation, mitochondrial dysfunction in microglial cells might contribute to the detrimental effects of neuroinflammation seen in neurodegenerative diseases.
Ferger
Annette I
AI
Department of Neurology, Ulm University, Germany.
Campanelli
Loretta
L
Reimer
Valentina
V
Muth
Katharina N
KN
Merdian
Irma
I
Ludolph
Albert C
AC
Witting
Anke
A
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D016207:Cytokines; D008070:Lipopolysaccharides; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D014475:Uncoupling Agents; D012402:Rotenone; D007334:Insulin-Like Growth Factor I; C015392:3-nitropropionic acid