Differential expression, shedding, cytokine regulation and function of TNFR1 and TNFR2 in human fetal astrocytes

Sun Ju Choi, Kyoung Ho Lee, Hyun Sook Park, Soo Ki Kim, Choon Myung Koh, Joo Young Park

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-α induces pleiotropic cellular effects through a 55kDa, type 1 receptor (TNFR1) and a 75kDa type 2 receptor (TNFR2). Moreover, it participates in the pathogenesis of several CNS diseases, including demyelinating diseases. TNF-α receptors are differentially expressed and are regulated in many cell types. However, data regarding the TNF-α receptor expression and regulation in human astrocytes is limited to date. We investigated TNF-α receptor expression, its regulation by cytokines, and its functional role in primary cultured human fetal astrocytes, which are the most abundant cellular population in the central nervous system and are known to be immunologically active. In this study, astrocytes were found to constitutively and predominantly transcribe, translate and shed TNFR1 rather than TNFR2, but TNFR2 expression was increased by adding TNF-α, IL-1, and IFN-γ, but not by adding LPS. To determine the functional roles of TNFR1 and TNFR2 on TNF induction,we investigated NF-κB activation and TNF-α induction after neutralizing TNFR1 and TNFR2 by an antibody treatment. We found that NF-κB activation and TNF-α induction are blocked by TNFR1 neutralizing antibody treatments.

Original languageEnglish
Pages (from-to)818-826
Number of pages9
JournalYonsei medical journal
Volume46
Issue number6
DOIs
Publication statusPublished - 2005 Dec

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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