Th1/Th2 imbalance and heat shock protein mediated inflammatory damage triggered by manganese via activating NF-κB pathway in chicken nervous system in vivo and in vitro

Manganese (Mn) is a ubiquitous heavy metal pollutant in environment, and excess Mn can damage nervous system of humans and animals. However, molecular mechanism of Mn-induced poultry neurotoxicity on inflammatory injury is still not fully clear. Thus, the purpose of the conducted research was to explore molecular mechanism of inflammatory injury caused by Mn in chicken nervous system. Two Mn poisoning models were established in vivo and in vitro. One hundred and eighty chickens were randomly separated into four groups. One control group was raised drinking water and standard diet. Three Mn groups were raised drinking water, and the standard diet supplemented with three different concentrations of MnCl2 center dot 4H(2)O. There were 45 birds and 3 replicates in each group. Neurocytes from chicken embryos were cultured in mediums without and with six different concentrations of MnCl2 center dot 4H(2)O in vitro. Our experiments showed that excess Mn caused cerebral histomorphological structure alternations and damage, and increased the expressions (P < 0.05) of inflammation-related factor NF-kappa B, TNF-alpha, iNOS, COX-2, and PTGEs in vivo and in vitro, meaning that excess Mn caused inflammatory damage and inflammatory response in chicken nervous system. Moreover, there were an upregulated IFN-gamma mRNA expression and a downregulated IL-4 mRNA expression (P < 0.05) in bird cerebra and embryonic neurocytes after exposure to Mn, indicating that Mn exposure caused Th1/Th2 imbalance and immunosuppression. Additionally, in our research, the elevation (P < 0.05) of five HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90) was found, suggesting that HSPs participated molecular mechanism of Mn stress. In addition, the inflammatory toxicity of Mn to chicken nervous system was time- and dose-dependent. Taken all together, our findings indicated that Th1/Th2 imbalance and HSPs mediated Mn-caused inflammatory injury via NF-kappa B pathway in chicken nervous system in vivo and in vitro.