Osteopontin directly modulates cytokine expression of primary microglia and increases their survival

• Osteopontin (OPN) enhances microglia survival under stress conditions (serum-free medium)
• OPN dose-dependently abrogates LPS-induced release of nitric oxide and pro-inflammatory cytokines
• OPN exerts anti-inflammatory functions in a moderate inflammatory environment, but does not counteract severe inflammation
• OPN modulates microglia function by shifting their inflammatory profile towards a neutral phenotype

Osteopontin (OPN) is constitutively expressed in the brain and upregulated during neuroinflammation, e.g., focal cerebral ischemia. In OPN-deficient mice, microglia are deregulated after ischemia, but specific OPN-effects on microglia remain elusive.Primary microglia were cultured in the presence or absence of OPN. The survival of microglia under stress conditions was dose-dependently increased by OPN. Lipopolysaccharides (LPS)-induced release of nitric oxide (NO), TNF-α, and IL-6, as well as expression of inducible Nitric Oxide Synthase (iNOS), were attenuated by OPN. Data suggest that OPN modulates microglia function by shifting their inflammatory profile towards a neutral anti-inflammatory phenotype.

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