| First Author | Yao J | Year | 1997 |
| Journal | Brain Res Mol Brain Res | Volume | 51 |
| Issue | 1-2 | Pages | 170-8 |
| PubMed ID | 9427519 | Mgi Jnum | J:46717 |
| Mgi Id | MGI:1201871 | Doi | 10.1016/s0169-328x(97)00235-0 |
| Citation | Yao J, et al. (1997) Induction of interleukin-1 beta-converting enzyme (ICE) in murine microglia by lipopolysaccharide. Brain Res Mol Brain Res 51(1-2):170-8 |
| abstractText | Interleukin-1beta (IL-1beta) synthesized in the brain is thought to be involved in the behavioral response to LPS. In this study, we examined in microglia the ability of LPS to induce interleukin-1 beta-converting enzyme (ICE), the protease responsible for processing proIL-1beta to its mature biologically active form. The murine microglial cell line, N13, and primary microglia which had been previously isolated from brains of 2-d-old endotoxin-responsive C3H/HeOuJ mice and endotoxin-resistant C3H/HeJ mice, were cultured in the presence of various concentrations of LPS. Oligonucleotide primers for ICE and GAPDH were used in RT-PCR to determine the levels of ICE mRNA in microglia. ICE mRNA was constitutively expressed in N13 cells and primary microglia from both C3H/HeOuJ and C3H/HeJ mice. Upon exposure to LPS, ICE mRNA levels were markedly elevated in N13 cells and in microglia from C3H/HeOuJ mice, but not in microglia from endotoxin-resistant C3H/HeJ mice. Western immunoblotting was used to determine if the increase in ICE mRNA induced by LPS was accompanied by an increase in ICE protein. A modest increase in immunoreactivity for the p45 ICE precursor protein was evident in N13 cells and primary microglia from C3H/HeOuJ mice following exposure to LPS. Because corticosteroids inhibit the synthesis and secretion of IL-1beta, in a second experiment microglia were treated with LPS in the presence of dexamethasone (0, 10 and 100 microM). Dexamethasone inhibited the LPS-induced increase in ICE mRNA and protein in microglia from C3H/HeOuJ mice. These results indicate that LPS stimulates microglia to express ICE. That dexamethasone inhibited the expression of ICE, suggests that corticosteroids regulate the secretion of IL-1beta by microglial cells, in part, by regulating the expression of ICE. |
