| First Author | Komiya H | Year | 2021 |
| Journal | Mol Brain | Volume | 14 |
| Issue | 1 | Pages | 74 |
| PubMed ID | 33931083 | Mgi Jnum | J:306998 |
| Mgi Id | MGI:6705137 | Doi | 10.1186/s13041-021-00785-8 |
| Citation | Komiya H, et al. (2021) Ablation of interleukin-19 improves motor function in a mouse model of amyotrophic lateral sclerosis. Mol Brain 14(1):74 |
| abstractText | Neuroinflammation by activated microglia and astrocytes plays a critical role in progression of amyotrophic lateral sclerosis (ALS). Interleukin-19 (IL-19) is a negative-feedback regulator that limits pro-inflammatory responses of microglia in an autocrine and paracrine manner, but it remains unclear how IL-19 contributes to ALS pathogenesis. We investigated the role of IL-19 in ALS using transgenic mice carrying human superoxide dismutase 1 with the G93A mutation (SOD1(G93A) Tg mice). We generated IL-19-deficient SOD1(G93A) Tg (IL-19(-/-)/SOD1(G93A) Tg) mice by crossing SOD1(G93A) Tg mice with IL-19(-/-) mice, and then evaluated disease progression, motor function, survival rate, and pathological and biochemical alternations in the resultant mice. In addition, we assessed the effect of IL-19 on glial cells using primary microglia and astrocyte cultures from the embryonic brains of SOD1(G93A) Tg mice and IL-19(-/-)/SOD1(G93A) Tg mice. Expression of IL-19 in primary microglia and lumbar spinal cord was higher in SOD1(G93A) Tg mice than in wild-type mice. Unexpectedly, IL-19(-/-)/SOD1(G93A) Tg mice exhibited significant improvement of motor function. Ablation of IL-19 in SOD1(G93A) Tg mice increased expression of both neurotoxic and neuroprotective factors, including tumor necrosis factor-alpha (TNF-alpha), IL-1beta, glial cell line-derived neurotrophic factor (GDNF), and transforming growth factor beta1, in lumbar spinal cord. Primary microglia and astrocytes from IL-19(-/-)/SOD1(G93A) Tg mice expressed higher levels of TNF-alpha, resulting in release of GDNF from astrocytes. Inhibition of IL-19 signaling may alleviate ALS symptoms. |
