Roles of NF-kappaB and MAPK signaling pathways in morphological and cytoskeletal responses of microglia to double-stranded RNA

• Published in: Neuroscience letters Vol. 414; no. 3; pp. 222 - 227
• Main Authors: Nakamichi, Kazuo, Saiki, Megumi, Kitani, Hiroshi, Kuboyama, Yuki, Morimoto, Kinjiro, Takayama-Ito, Mutsuyo, Kurane, Ichiro
• Format: Journal Article
• Language: English
• Published: Ireland 13.03.2007
• Subjects: Actins - genetics; Actins - immunology; Actins - metabolism; Animals; Animals, Newborn; Cell Line, Transformed; Cell Shape - genetics; Cell Shape - immunology; Cytoskeleton - genetics; Cytoskeleton - immunology; Cytoskeleton - metabolism; Encephalitis - genetics; Encephalitis - immunology; Encephalitis - metabolism; Gliosis - genetics; Gliosis - immunology; Gliosis - metabolism; Humans; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - immunology; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System - genetics; MAP Kinase Signaling System - immunology; Mice; Mice, Inbred C57BL; Microglia - drug effects; Microglia - immunology; Microglia - metabolism; NF-kappa B - immunology; NF-kappa B - metabolism; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - immunology; p38 Mitogen-Activated Protein Kinases - metabolism; RNA Virus Infections - genetics; RNA Virus Infections - immunology; RNA Virus Infections - metabolism; RNA, Double-Stranded - genetics; RNA, Double-Stranded - pharmacology; Vacuoles - genetics; Vacuoles - immunology; Vacuoles - metabolism
• ISSN: 0304-3940

Following virus infection of the central nervous system, microglia become activated and undergo morphological as well as functional transformations, thereby initiating effective antiviral actions. Herein, we have examined the contribution of nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways to cell shape determination and cytoskeletal organization in microglia upon stimulation with double-stranded RNA (dsRNA), a conserved molecular pattern of virus infection. Under non-proliferative condition, microglial MG6-1 cells displayed a distinctive morphology with spinescent processes and small somata. Following dsRNA stimulation, the process-bearing microglial cells exhibited swift and drastic changes in cell morphology, filamentous actin (F-actin) structure, and intracellular signaling. In the dsRNA-stimulated microglial cells, the activation of c-Jun N-terminal kinase (JNK) pathway was involved in morphological alteration into an ameboid state. We also found that p38 signaling pathway negatively regulates the formation of cytoplasmic vacuoles in microglial cells. Furthermore, the dsRNA-induced accumulation of F-actin was partly mediated by NF-kappaB, JNK, and p38 pathways. These results indicate that NF-kappaB and MAPK signaling pathways mediate morphological and cytoskeletal changes during dsRNA-induced microglial activation.