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

Abstract 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.