A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia

Shinrye Lee, Jayoung Lee, Sangseop Kim, Jae-Yong Park, Won Ha Lee, Kiyoshi Mori, Sang Hyun Kim, Kyeom Kim In, Kyoungho Suk

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Activated microglia are thought to undergo apoptosis as a self-regulatory mechanism. To better understand molecular mechanisms of the microglial apoptosis, apoptosis-resistant variants of microglial cells were selected and characterized. The expression of lipocalin 2 (lcn2) was significantly down-regulated in the microglial cells that were resistant to NO-induced apoptosis. lcn2 expression was increased by inflammatory stimuli in microglia. The stable expression of lcn2 as well as the addition of rLCN2 protein augmented the sensitivity of microglia to the NO-induced apoptosis, while knockdown of lcn2 expression using short hairpin RNA attenuated the cell death. Microglial cells with increased lcn2 expression were more sensitive to other cytotoxic agents as well. Thus, inflammatory activation of microglia may lead to up-regulation of lcn2 expression, which sensitizes microglia to the self-regulatory apoptosis. Additionally, the stable expression of lcn2 in BV-2 microglia cells induced a morphological change of the cells into the round shape with a loss of processes. Treatment of primary microglia cultures with the rLCN2 protein also induced the deramification of microglia. The deramification of microglia was closely related with the apoptosis-prone phenotype, because other deramification-inducing agents such as cAMP-elevating agent forskolin, ATP, and calcium ionophore also rendered microglia more sensitive to cell death. Taken together, our results suggest that activated microglia may secrete LCN2 protein, which act in an autocrine manner to sensitize microglia to the self-regulatory apoptosis and to endow microglia with an amoeboid form, a canonical morphology of activated microglia in vivo.

Original languageEnglish
Pages (from-to)3231-3241
Number of pages11
JournalJournal of Immunology
Volume179
Issue number5
DOIs
Publication statusPublished - 2007 Sep 1
Externally publishedYes

Fingerprint

Microglia
Apoptosis
Lipocalin-2
Cell Death
Proteins
Calcium Ionophores
Cytotoxins
Colforsin
Small Interfering RNA
Up-Regulation
Adenosine Triphosphate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia. / Lee, Shinrye; Lee, Jayoung; Kim, Sangseop; Park, Jae-Yong; Lee, Won Ha; Mori, Kiyoshi; Kim, Sang Hyun; In, Kyeom Kim; Suk, Kyoungho.

In: Journal of Immunology, Vol. 179, No. 5, 01.09.2007, p. 3231-3241.

Research output: Contribution to journalArticle

Lee, S, Lee, J, Kim, S, Park, J-Y, Lee, WH, Mori, K, Kim, SH, In, KK & Suk, K 2007, 'A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia', Journal of Immunology, vol. 179, no. 5, pp. 3231-3241. https://doi.org/10.4049/jimmunol.179.5.3231
Lee, Shinrye ; Lee, Jayoung ; Kim, Sangseop ; Park, Jae-Yong ; Lee, Won Ha ; Mori, Kiyoshi ; Kim, Sang Hyun ; In, Kyeom Kim ; Suk, Kyoungho. / A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia. In: Journal of Immunology. 2007 ; Vol. 179, No. 5. pp. 3231-3241.
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