Alterations in splenocyte protein kinase C (PKC) activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vivo

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on growth factor-coupled activation of nuclear protein kinase C (nPKC) and on the subcellular distribution of PKC activity in rat splenocytes were investigated. Seven days after a single injection of TCDD (50 micrograms/kg body weight), cytosolic and particulate PKC activity was significantly higher in splenocytes from TCDD-treated rats or pair-fed control rats compared to ad libitum-fed animals. In a separate experiment, purified splenocyte nuclei from TCDD-treated animals and controls were used to study activation of nPKC by growth factors and other trophic agents. Growth factor-stimulated nPKC activation was attenuated in splenic nuclei from TCDD-treated rats compared to vehicle-treated controls. Evidence presented here suggests that the cellular mechanism of TCDD toxicity leading to immunosuppression in rodents may be mediated in part by uncoupling of growth factor receptors linked to PKC activation at the level of the nucleus. However, changes in total splenocyte PKC activity appear to be correlated with hypophagia since cytosolic and particulate PKC levels were elevated in TCDD-treated rats and their pair-fed partners.