CYTOKINE INDUCTION OF HEAT-SHOCK PROTEIN EXPRESSION IN HUMAN OLIGODENDROCYTES - AN INTERLEUKIN-1-MEDIATED MECHANISM

In this study, we examined the role of cytokines, known to be in eleva ted levels in multiple sclerosis (MS) plaques, in regulating oligodend rocyte (ODC) expression of heat shock protein (hsp) in human brain-der ived glial cell cultures. Using dual-stain immunohistochemistry, we in itially compared the ability of a mixture of cytokines (IL-1 alpha, IL -1 beta, IL-2, IL-6, IL-8, TNF-alpha, TNF-beta, IFN-beta, IFN-gamma) w ith that of physical stimuli such as heat shock and peroxide, to incre ase cellular expression of the mainly inducible hsp72 species in mixed glial cell cultures (containing ODC, astrocytes and microglia). Simil ar to heat shock and peroxide, the cytokine mixture induced hsp72 expr ession only in ODC (70 +/- 5% vs. a baseline of 3 +/- 1% positive cell s). When used individually, however, only IL-1 alpha (79 +/- 3%), IFN- gamma (70 +/- 2%) and TNF-alpha (65 +/- 5%) induced ODC hsp72 expressi on in mixed glial cell cultures. In purified ODC preparations, only IL -1 alpha induced hsp72 expression (84 +/- 4%), an IL-1 receptor antago nist (IL-1ra), abrogated hsp72 induction by IL-la (16 +/- 3%) as well as that due to IFN-gamma (14 +/- 1%) and TNF-alpha (13 +/- 2%) (13 +/- 2%) in mixed glial cell cultures. Furthermore, ODC express IL-1 recep tors, detected by confocal laser scanning microscopy. Our data indicat e that cytokines mediate hsp induction in ODC possibly via a final com mon pathway involving IL-1 binding to its receptor on ODC. Such intera ction could enhance any putative ODC-immune interactions which are dep endent on hsp molecule recognition.