Ammonia Attenuates LPS-Induced Upregulation of Pro-Inflammatory Cytokine mRNA in Co-Cultured Astrocytes and Microglia

Abstract

Hepatic encephalopathy (HE) is associated with cerebral microglia activation. Ammonia, a major toxin of HE, activates microglia in vitro but does not trigger pro-inflammatory cytokine synthesis. In the present study we analysed effects of ammonia on lipopolysaccharide (LPS)-induced upregulation of microglia activation and cytokine mRNA as well as on cytokine secretion in mono-cultured microglia and co-cultured astrocytes and microglia. In mono-cultured microglia LPS (100 ng/ml, 18 h) strongly elevated mRNA levels of the microglia activation marker CD14 and the pro-inflammatory cytokines IL-1/, IL-6 and TNF-. NH4Cl (5 mmol/l) had no effect on LPS-induced upregulation of CD14, IL-1/ and IL-6 mRNA but enhanced LPS-induced upregulation of TNF- mRNA in mono-cultured microglia. In co-cultured astrocytes and microglia, however, LPS-induced upregulation of IL-1/, TNF-, IL-6, CD14 but not of IL-10, IL-12A/B or TGF1-3 mRNA was attenuated by NH4Cl. LPS-induced upregulation of IL-1/, I