Ibuprofen and apigenin induce apoptosis and cell cycle arrest in activated microglia.
In case of injury or disease, microglia are recruited to the site of the pathology and become activated as evidenced by morphological changes and expression of pro-inflammatory cytokines. Evidence suggests that microglia proliferate by cell division to create gliosis at the site of pathological conditions such as the amyloid plaques in Alzheimer's disease and the substantia nigra of Parkinson's disease patients. The hyperactivation of microglia contributes to neurotoxicity. In the present study we tested the hypothesis that anti-inflammatory compounds modulate the progression of cell cycle and induce apoptosis of the activated cells. We investigated the effects of ibuprofen (non-steroidal anti-inflammatory drug) and apigenin (a flavonoid with anti-inflammatory and anti-proliferative properties) on the cell cycle of the murine microglial cell line BV-2. The findings indicate that apigenin-induced cell cycle arrest preferentially in the G2/M phase and ibuprofen caused S phase arrest. The binding of annexin V-FITC to the membranes of cells which indicates the apoptotic process were examined, whereas the DNA was stained with propidium iodide. Both apigenin and ibuprofen induced apoptosis significantly in early and late stages. The induction of apoptosis by ibuprofen and apigenin was confirmed using TUNEL assay, revealing that 25 microM apigenin and 250 microM ibuprofen significantly increased apoptosis in BV-2 cells. The results from the present study suggest that anti-inflammatory compounds might inhibit microglial proliferation by modulating the cell cycle progression and apoptosis.
Elsisi
Nahed S
NS
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahaeess, FL 32307, USA.
Darling-Reed
Selina
S
Lee
Eunsook Y
EY
Oriaku
Ebenezer T
ET
Soliman
Karam F
KF
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D047310:Apigenin / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D005911:Gliosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D007052:Ibuprofen / Q000494:pharmacology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011419:Propidium; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D017304:Annexin A5; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011419:Propidium; D047310:Apigenin; D016650:Fluorescein-5-isothiocyanate; D007052:Ibuprofen