IL-1beta enhances the antibacterial activity of astrocytes by activation of NF-kappaB.
Astrocytes have important immune functions in CNS, and astrocytes stimulated by interferon-gamma were showed to have direct antimicrobial function. However whether astrocytes without the stimulation of cytokines have antibacterial function, and how this function is regulated are still largely unknown. In this study, we found that primary cultured astrocytes inhibited the growth of both gram-negative and gram-positive bacteria. Further more, we showed that interleukin-1beta (IL-1beta) enhanced the antibacterial effect in a dose-dependent manner, and the antibacterial effect of astrocytes from IL-1beta receptor-deficient mice failed to be enhanced by IL-1beta. IL-1beta stimulated IkappaBalpha degradation, NF-kappaB nuclear translocation, and transactivation in astrocytes. NF-kappaB inhibitors blocked NF-kappaB activation and the enhanced antibacterial effect induced by IL-1beta. In addition, overexpression of dominant negative IkappaBalpha in astrocytes inhibited IkappaBalpha degradation and NF-kappaB transactivation, and also inhibited the enhanced antibacterial effect induced by IL-1beta. All these data demonstrated that IL-1beta enhanced the antibacterial activity of astrocytes by activation of NF-kappaB.
Xia
Yulei
Y
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Zhai
Qiwei
Q
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D006090:Gram-Negative Bacteria / Q000502:physiology*; D006094:Gram-Positive Bacteria / Q000502:physiology*; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics
D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D053573:Receptors, Interleukin-1 Type I; D000072000:NF-KappaB Inhibitor alpha