| First Author | Tian Z | Year | 2020 |
| Journal | Mol Neurobiol | Volume | 57 |
| Issue | 10 | Pages | 4069-4081 |
| PubMed ID | 32661728 | Mgi Jnum | J:318040 |
| Mgi Id | MGI:6860573 | Doi | 10.1007/s12035-020-02003-3 |
| Citation | Tian Z, et al. (2020) Platelet-Activating Factor Deteriorates Lysophosphatidylcholine-Induced Demyelination Via Its Receptor-Dependent and -Independent Effects. Mol Neurobiol 57(10):4069-4081 |
| abstractText | Accumulating evidence suggests that platelet-activating factor (PAF) increases the inflammatory response in demyelinating diseases such as multiple sclerosis. However, PAF receptor (PAFR) antagonists do not show therapeutic efficacy for MS, and its underlying mechanisms remain poorly understood. In the present study, we investigated the effects of PAF on an ex vivo demyelination cerebellar model following lysophosphatidylcholine (LPC, 0.5 mg/mL) application using wild-type and PAFR conventional knockout (PAFR-KO) mice. Demyelination was induced in cerebellar slices that were cultured with LPC for 18 h. Exogenous PAF (1 muM) acting on cerebellar slices alone did not cause demyelination but increased the severity of LPC-induced demyelination in both wild-type and PAFR-KO mice. LPC inhibited the expression of PAF-AH, MBP, TNF-alpha, and TGF-beta1 but facilitated the expression of IL-1beta and IL-6 in wild-type preparations. Of note, exogenous PAF stimulated microglial activation in both wild-type and PAFR-KO mice. The subsequent inflammatory cytokines TNFalpha, IL-1beta, and IL-6 as well as the anti-inflammatory cytokine TGF-beta1 demonstrated a diverse transcriptional profile with or without LPC treatment. PAF promoted TNF-alpha expression and suppressed TGF-beta1 expression indiscriminately in wild-type and knockout slices; however, transcription of IL-1beta and IL-6 was not significantly affected in both slices. The syntheses of IL-1beta and IL-6 were significantly increased in LPC-induced demyelination preparations without PAF but showed a redundancy in PAF-treated wild-type and knockout slices. These data suggest that PAF can play a detrimental role in LPC-induced demyelination probably due to a redundant response of PAFR-dependent and PAFR-independent effects on inflammatory cytokines. |
