PKC and tyrosine kinase involvement in amyloid β (25-35)-induced chemotaxis of microglia

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Abstract

MICROGLIA are activated by amyloid β (Aβ) in vivo and in vitro, and Aβ-activated microglia may be involved in the pathogenesis of Alzheimer's disease (AD). We investigated the mechanism of microglial chemotaxis induced by Aβ (25–35), an active fragment of Aβ. Aβ (25–35) 0.1 and 1 nM stimulated microglial chemotaxis. The protein kinase C (PKC) inhibitors chelerythrine (0.5 and 2 μM), calphostin C (1 μM) and staurospine (10 nM) significantly inhibited the microglial chemotaxis induced by Aβ (25–35) (1 nM). The chemotactic effect of Aβ (25–35) on microglia was desensitized by pretreatment of microglia with 1 ng/ml 12-O-tetrade-canoylphorbol 13-acetate (TPA). Pretreatment of cells with Aβ (25–35) (1 nM) also desensitized the chemotactic effect by Aβ (25–35) (1 nM). The desensitization by TPA or Aβ (25–35) was inhibited when staurosporine was present in the pretreatment media. The tyrosine kinase inhibitor herbimycin A (0.1 and 1 μM) significantly inhibited the microglial chemotaxis induced by Aβ (25–35) (1 nM). Based on these observations, it seems likely that PKC and tyrosine kinase are involved in the Aβ-induced chemotaxis of microglia.

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