TY - JOUR
T1 - The iNOS/Src/FAK axis contributes to lithium chloride-mediated macrophage migration
AU - Chen, Hui Chen
AU - Chien, Wan Chu
AU - Chang, Miao Ying
AU - Hsieh, Ming Yu
AU - Lai, Ming Der
AU - Maa, Ming Chei
AU - Leu, Tzeng Horng
N1 - Funding Information:
This work is supported in part by National Health Research Institute Grant NHRI-EX103-10131BI (to T.-H.L.); National Science Council Taiwan Grants NSC102-2325-B-006-010 (to T.-H.L.) and NSC101-2311-B-039-002-MY3 (to M.-C.M.); Taiwan Department of Health Clinical Trial and Research Center of Excellence Grant DOH103-TD-B-111-004 (to M.-C.M.); and China Medical University Grant CMU101-S-02 (to M.-C.M.).
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Lithium chloride (LiCl) has long been used as a mood stabilizer for bipolar mood depression patients. However, its biological effects on immune cells are unclear yet. In this study, we observed that upon LiCl stimulation, the motility and the content of total protein tyrosine phosphorylation in RAW264.7 macrophages and murine peritoneal macrophages (PEMs) were significantly increased. The inhibition of LiCl-induced macrophage migration by PP2 (an inhibitor for Src family kinases (SFKs)) suggested the involvement of SFKs in this process. Interestingly, LiCl induced NF-kB activation, and while Src was greatly induced, the expression of its myeloid relatives (i.e. Lyn, Fgr, Hck) was almost unaltered in RAW264.7 cells. Knockdown of Src suppressed LiCl-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by siRNA-resistant Src. Consistent with Src and migration increment was iNOS-dependent in macrophages, markedly reduced Src expression, activity and cell migration were observed in iNOS-null PEMs treated with LiCl. Moreover, FAK knockdown suppressed LiCl-stimulated macrophage motility, suggesting the involvement of FAK in this process. Remarkably, similar increment of iNOS, Src, FAK Pi-Tyr861 and migration ability could also be detected in RAW264.7 treated with other GSK3β inhibitors (i.e. SB216763 and Kenpaullone). These results corroborate that through inhibition of GSK3β, the iNOS/Src/FAK axis occupies a critical role in macrophage locomotion in response to LiCl.
AB - Lithium chloride (LiCl) has long been used as a mood stabilizer for bipolar mood depression patients. However, its biological effects on immune cells are unclear yet. In this study, we observed that upon LiCl stimulation, the motility and the content of total protein tyrosine phosphorylation in RAW264.7 macrophages and murine peritoneal macrophages (PEMs) were significantly increased. The inhibition of LiCl-induced macrophage migration by PP2 (an inhibitor for Src family kinases (SFKs)) suggested the involvement of SFKs in this process. Interestingly, LiCl induced NF-kB activation, and while Src was greatly induced, the expression of its myeloid relatives (i.e. Lyn, Fgr, Hck) was almost unaltered in RAW264.7 cells. Knockdown of Src suppressed LiCl-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by siRNA-resistant Src. Consistent with Src and migration increment was iNOS-dependent in macrophages, markedly reduced Src expression, activity and cell migration were observed in iNOS-null PEMs treated with LiCl. Moreover, FAK knockdown suppressed LiCl-stimulated macrophage motility, suggesting the involvement of FAK in this process. Remarkably, similar increment of iNOS, Src, FAK Pi-Tyr861 and migration ability could also be detected in RAW264.7 treated with other GSK3β inhibitors (i.e. SB216763 and Kenpaullone). These results corroborate that through inhibition of GSK3β, the iNOS/Src/FAK axis occupies a critical role in macrophage locomotion in response to LiCl.
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U2 - 10.1016/j.niox.2015.04.001
DO - 10.1016/j.niox.2015.04.001
M3 - Article
C2 - 25870166
AN - SCOPUS:84928529138
VL - 47
SP - 58
EP - 64
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
SN - 1089-8603
ER -