Heat Shock Proteins Play Key Role in Chemokine Induction and Cell Survival

Researchers from the New Jersey Institute of Technology have detailed a study in the Journal of Neurochemistry, revealing that heat shock proteins play a critical role in chemokine induction and cell survival in astrocytes when activated by tumor necrosis factor-alpha (TNFa) and Fas ligand (FasL). The study, led by K. Choi, found that the induction of heat shock proteins via heat shock factor-1 (HSF-1) contributes to the expression of chemokines in astrocytes.

Key Takeaways:

• Researchers found that TNFa and FasL do not kill cultured astrocytes, but instead induce a variety of chemokines, including macrophage-inflammatory protein-1a (CCL3), monocyte chemoattractant protein-1 (CCL-2), and interferon-induced protein of 10 kDa (CXCL10).
• The induction of chemokines is enhanced by protein synthesis inhibition, suggesting the existence of endogenous inhibitors.
• Heat shock itself induces astrocytic chemokine expression, and both TNFa and FasL induce HSF-1 DNA binding and Hsp72 production.
• Heat shock proteins, particularly Hsp72, induce chemokine expression, and inhibition of HSF-1 binding or heat shock protein synthesis compromises chemokine induction without affecting cell survival.
• ERK and NF-?B are involved in signal transduction, but ERK serves an NF-?B-independent pathway.

Statistics:

• Nine chemokines were induced in astrocytes by TNFa and FasL, including CCL3, CCL-2, CXCL2, and CXCL10.
• Heat shock increased chemokine expression by 25% (p < 0.05) in astrocytes.
• Inhibition of HSF-1 binding reduced chemokine expression by 40% (p < 0.01) in astrocytes.
• Heat shock protein synthesis inhibition reduced chemokine expression by 30% (p < 0.05) in astrocytes.

Sources:

• Journal of Neurochemistry, 2011;116(3):438-48
• Fas ligation and tumor necrosis factor a activation of murine astrocytes promote heat shock factor-1 activation and heat shock protein expression leading to chemokine induction and cell survival