Retinoic acid enhances leukemia inhibitory factor expression in OLN-93 oligodendrocytes

Abstract

Brain injuries trigger physiological reactions which are mediated by a number of cytokines including interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF). Astrocytes and microglia, the protagonists in these traumatic responses, are known to secrete a variety of paracrine signals. Oligodendrocytes are involved as well and constitute another possible source of cytokines. Here we show the expression of IL-6, CNTF, and LIF in OLN-93 cells, derived from rat oligodendrocyte primary cultures. While differential gene transcription after injury has been described for many cytokines, the regulation of these physiological responses is unknown in many instances. Recent experiments indicate that the transcriptional activator retinoic acid (RA) plays a role in peripheral nerve regeneration. Transcripts of the retinoic acid receptors and the retinoid X receptors were also detected in OLN-93 oligodendrocytes. Using quantitative RT-PCR, we have therefore investigated the effect of RA on the expression of neuropoietic cytokines in these cells. Treatment with 1 microM all- trans RA for 24 h increased the mRNA concentration of LIF by a factor of 3.1 ( P<0.01). In contrast, RA had no significant effect on the expression of CNTF. The results suggest RA as a possible regulator of cytokine signaling in the CNS.

LIF in the regulation of T-cell fate and as a potential therapeutic

“…As ATRA promotes the Treg lineage, 81,82,84,[86][87][88] it is worth asking, is there any evidence for cross-regulation between ATRA and LIF? Importantly, LIF influences oxidative conversion of vitamin A to ATRA in mouse embryonic stem cell; 89 also, LIF synergises with ATRA in differentiation of neural precursor cells to astrocytes 90 and ATRA induces LIF expression in oligodendrocytes: 91 furthermore LIF is induced by ATRA in mouse embryonic stem cell. 92 Taken together these observations indicate inter-relationships between ATRA and LIF and convergent pathways on epigenetic development.…”

New therapeutic target for CNS injury? The role of retinoic acid signaling after nerve lesions

“…Immunohistochemical analyses reveal that activated microglia/macrophages and neurons express RAR and all RXRs, and that the contusion injury induces intracellular translocation of RAR, RXR, and RXR from a cytosolic to a nuclear expression in these cells (Schrage et al, 2006). Investigations with primary cultures show that other cell types including astrocytes (Ahlemeyer et al, 2000), oligodendrocytes (Mey and Henkes, 2002), and NG2 cells (Kern et al, unpublished data) should be considered as potential targets as well. Empirical findings that shed light on the possible functions of RA will now be discussed in the context of three processes: neural regeneration, inflammatory reaction, and glial activation (Fig.…”

Secretome Analysis of Human Oligodendrocytes Derived from Neural Stem Cells

“…IL-6 is expressed in oligodendrocytes [46], but the secretion of IL-6 from oligodendrocyte-lineage cells is not previously reported. IL-6 signaling induces the differentiation of oligodendrocyte precursor cells into oligodendrocytes and promotes their survival [43]–[45], [87].…”

“…Oligodendrocytes express IL6 receptors, and the addition of external IL6/IL6R fusion protein promotes oligodendrocyte differentiation from oligodendrocyte progenitor cells (OPCs), as well as oligodendrocyte survival [43]–[45]. However, although IL-6 is expressed in rat oligodendrocytes treated with retinoic acid [46], there are no previous reports of IL6 secretion from human oligodendrocytes. Second, CXCR2 and its ligands, including CXCL1 (Groα), CXCL2 (Groβ), CXCL3 (Groγ), CXCL5 (ENA-78), CXCL6 (GCP-2), and IL8, were upregulated in F3.Olig2 cells (Fig.…”

“…5C, Table 1). The first group includes proteins expressed in oligodendrocytes: Chordin-like 1 [60], IL-6 [46], IGFBP-6 [61], Galectin-3 [62], GRO [63], MMP-3 [64], MMP-9 [65], [66], and MMP-12 [67], [68]. Although IL-6, IGFBP-6, Galectin-3, GRO, and MMP-3 are known to be expressed at the mRNA or protein level in oligodendrocytes, this is the first report that these proteins are secreted from human oligodendrocytes.…”