First Author | Sung HY | Year | 2019 |
Journal | J Neurochem | Volume | 150 |
Issue | 6 | Pages | 691-708 |
PubMed ID | 31165473 | Mgi Jnum | J:280805 |
Mgi Id | MGI:6364698 | Doi | 10.1111/jnc.14788 |
Citation | Sung HY, et al. (2019) Down-regulation of interleukin-33 expression in oligodendrocyte precursor cells impairs oligodendrocyte lineage progression. J Neurochem 150(6):691-708 |
abstractText | Interleukin-33 (IL-33), a member of the IL1 family, has been found to be expressed in oligodendrocytes (OLGs) and released as an alarmin from injured OLGs to work on other glial cell-types in the central nervous system. However, its functional role in OLGs remains unclear. Herein, we present that IL-33 was mainly expressed in the nucleus of CC1(+) -oligodendrocytes (OLGs) in mouse and rat corpus callosum, as well as NG2(+) -oligodendrocyte precursor cells (OPCs). The in vitro study indicated that the amount of IL-33 expressing in OPCs was higher when compared to that detected in OLGs. Results from the experiments using lentivirus-mediated shRNA delivery against IL-33 expression (IL33-KD) in OPCs showed that IL33-KD reduced the differentiation of OLGs into mature OLGs along with the down-regulation of OLG differentiation-related genes and mature OLG marker proteins, myelin basic protein (MBP) and proteolipid protein (PLP). Alternatively, we observed reduced differentiation of OLGs that were prepared from the brains of IL-33 gene knockout (IL33-KO) mice with anxiolytic-like behavior. Observations were correlated with the results showing lower levels of MBP and PLP in IL33-KO cultures than those detected in the control cultures prepared from wildtype (WT) mice. Transmission Electron Microscopy (TEM) analysis revealed that the myelin structures in the corpus callosum of the IL33-KO mice were impaired compared to those observed in the WT mice. Overall, this study provides important evidence that declined expression of IL-33 in OPCs suppresses the maturation of OLGs. Moreover, gene deficiency of IL-33 can disrupt OLG maturation and interfere with myelin compaction. Cover Image for this issue: doi: 10.1111/jnc.14522. |