Effects of inflammatory cytokines IL-1beta, IL-6, and TNFalpha on the intracellular localization of retinoid receptors in Schwann cells.

It was investigated whether retinoic acid (RA) and the proinflammatory cytokines IL-1beta, IL-6, and TNFalpha influence the intracellular distribution of retinoic acid receptors (RAR) and retinoid X receptors (RXR) in Schwann cells. This question arose because nuclear translocation of RARalpha, RXRalpha, and RXRbeta was observed after nerve injury, and because mutual interactions exist between the signal transduction pathways of RA and proinflammatory cytokines. Schwann cell primary cultures from the rat sciatic nerve were incubated with IL-1beta, IL-6, and TNFalpha, with all-trans RA and with a combination of IL-1beta and RA. After incubation periods ranging from 5 min to 5 h, the intracellular distributions of RARalpha, RARbeta, RXRalpha, and RXRbeta were analyzed. All three cytokines caused a shift of RARalpha from the cytosolic compartments into the cell nuclei. This was also observed with RA, and combining RA with IL-1beta produced an additive effect. IL-1beta and IL-6 also affected the distribution of RARbeta, although immunoreactivity of this receptor always remained stronger in the cytosol. No effect of the cytokines on RXRalpha or RXRbeta was observed, whereas RA treatment caused a stronger nuclear signal of both receptors. Effects on the subcellular localization of retinoid receptors may provide a link in a feedback loop between RA/RAR and cytokines.