| First Author | Choi K | Year | 2011 |
| Journal | J Neurochem | Volume | 116 |
| Issue | 3 | Pages | 438-48 |
| PubMed ID | 21114495 | Mgi Jnum | J:170249 |
| Mgi Id | MGI:4946142 | Doi | 10.1111/j.1471-4159.2010.07124.x |
| Citation | Choi K, et al. (2011) Fas ligation and tumor necrosis factor alpha activation of murine astrocytes promote heat shock factor-1 activation and heat shock protein expression leading to chemokine induction and cell survival. J Neurochem 116(3):438-48 |
| abstractText | Death-inducing ligands tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) do not kill cultured astrocytes; instead they induce a variety of chemokines including macrophage-inflammatory protein-1alpha/CC chemokine ligand 3 (CCL3), monocyte chemoattractant protein-1 (CC CCL-2), macrophage-inflammatory protein-2/CXC chemokine ligand 2 (CXCL2, a murine homologue of interleukin 8), and interferon-induced protein of 10 kDa (CXCL10). Induction is enhanced by protein synthesis inhibition suggesting the existence of endogenous inhibitors. ERK, NF-kappaB, heat shock factor-1 (HSF-1) and heat shock proteins were examined for their possible roles in signal transduction. Inhibition of ERK activation by PD98059 partially inhibited expression of all but FasL-induced CXCL10. Although inhibition of NF-kappaB DNA binding inhibited chemokine induction, PD98059 did not inhibit TNFalpha-induced NF-kappaB DNA binding suggesting that ERK serves an NF-kappaB-independent pathway. Heat shock itself induced astrocytic chemokine expression; both TNFalpha and FasL induced HSF-1 DNA binding and Hsp72 production; and Hsp72-induced chemokine expression. Inhibition of either HSF-1 binding with quercetin or heat shock protein synthesis with KNK437 compromised chemokine induction without compromising cell survival. These data suggest that the induction of heat shock proteins via HSF-1 contribute to the TNFalpha- and FasL-induced expression of chemokines in astrocytes. |
