title: Effect of CCL2 on BV2 microglial cell migration: Involvement of probable signaling pathways.
abstract: Microglia, the resident macrophages of the central nervous system, play a vital role in the regulation of innate immune function and neuronal homeostasis of the brain. Currently, much interest is being generated regarding the investigation of the microglial migration that results in their accumulation at focal sites of injury. Chemokines including CCL2 are known to cause the potential induction of migration of microglial cells, although the underlying mechanisms are not well understood. In the present study, using murine neonatal BV2 microglial cells as a model, we investigate the impact of CCL2 on the migration of microglial cells and address the probable molecular events within the cellular signaling cascades mediating CCL2-induced cell migration. Our results demonstrate concentration- and time-dependent induction of BV2 cell migration by CCL2 and reveal complex mechanisms involving the activation of MEK, ERK1/2, and Akt, and their cross-talk. In addition, we demonstrate that the MEK/ERK pathway activated by CCL2 treatment mediate p90RSK activation in BV2 cells. Moreover, our findings indicate that Akt, ERK1/2, and p90RSK are the downstream effectors of PI3K in the CCL2-induced signaling. Finally, phosphorylation of the transcription factors c-jun and ATF-1 is found to be a further downstream signaling cascade in the CCL2-mediated action. Our results suggest that CCL2-induced activation of c-jun and ATF-1 is likely to be linked to the MEK/ERK and PI3K signaling pathways, respectively. Taken together, these findings contribute to a better understanding of CCL2-induced microglial migration and the probable signaling pathways involved.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Shambhunath
authors.initials: S
authors.lastname: Bose
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Md
authors.initials: M
authors.lastname: Moniruzzaman
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Gyeongjun
authors.initials: G
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do 10326, Republic of Korea. Electronic address: neuroph@dongguk.edu.
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
mesh_terms: D051697:Activating Transcription Factor 1 / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D013997:Time Factors
chemical_list: D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D018932:Chemokine CCL2; D016755:Proto-Oncogene Proteins c-jun; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BV2 cells; CCL2; CCR2; Intracellular signaling pathways; Migration