Inflammation induces serine protease inhibitor 3 expression in the rat pineal gland

Neuroscience. 2002;113(2):387-94. doi: 10.1016/s0306-4522(02)00198-7.


In the rat pineal gland, prominent expression of serine protease inhibitor 3 (SPI-3) mRNA is seen after systemic injection of lipopolysaccharide. The up-regulation of SPI-3 mRNA expression is also confirmed by northern blotting. Most SPI-3 mRNA-positive cells simultaneously express synaptophysin, a marker for pinealocytes, but not glial fibrillary acidic protein, a marker for astrocytes. This indicates that SPI-3 mRNA-positive cells are pinealocytes. Almost all SPI-3 mRNA-positive cells also showed translocation of the signal transducers and activators of transcription 3 (STAT3) into nuclei after lipopolysaccharide injection. These data support previous in vitro results that SPI-3 expression is induced in a STAT3-mediated manner. In addition, the expression of ciliary neurotrophic factor receptor (CNTFR) and leukemia inhibitory factor receptor (LIFR) mRNAs, but not of interleukin 6 receptor mRNA, was up-regulated after systemic lipopolysaccharide treatment. Because these receptors are upstream of STAT3, the present results suggest that cytokines such as LIF and/or CNTF induce SPI-3 expression via STAT3 in the pineal gland in response to inflammatory stimulus. We conclude that although the functional consequences of SPI-3 in the pineal gland during systemic inflammation are unknown, SPI-3 may have a crucial role in preventing some degenerative proteolysis induced by inflammatory stimuli.

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Animals
  • DNA-Binding Proteins / metabolism
  • Immunohistochemistry
  • Inflammation / metabolism*
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Lipopolysaccharides / pharmacology
  • Male
  • Pineal Gland / cytology
  • Pineal Gland / drug effects
  • Pineal Gland / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Ciliary Neurotrophic Factor / genetics
  • Receptors, Cytokine / genetics
  • Receptors, OSM-LIF
  • STAT3 Transcription Factor
  • Serpins
  • Trans-Activators / metabolism


  • Acute-Phase Proteins
  • DNA-Binding Proteins
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Lifr protein, rat
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Cytokine
  • Receptors, OSM-LIF
  • STAT3 Transcription Factor
  • Serpina3n protein, rat
  • Serpins
  • Stat3 protein, rat
  • Trans-Activators