IL 2 regulates the transcription of a number of genes including the protooncogenes, c-fos, c-mvc, c-myb as well as other genes such as ornithine decarboxylase (ODC) and the IL 2 receptor alpha chain (Tac). Antiproliferative signals such as cyclic AMP selectively inhibit IL 2 directed increases in c-myc and ODC mRNA accumulation. The specific deletion of c-myc protein biosynthesis by synthetic """"""""anti-sense"""""""" oligonucleotides inhibited PHA or IL 2 directed proliferation of human T cells. IL 2 also stimulates mRNA expression and protein synthesis of ancient stress genes such as HSP-70. We have investigated the DNA binding proteins which recognize the enhancer regulatory element of the HSP-70 gene. We are likewise examining DNA binding proteins specific for the c-myc and IL 2 receptor enhancer sequences do determine what signals modulate the effects of these proteins on their respective gene transcription. We have shown that human T lymphocytes synthesize pro- opiomelanocortin (POMC) mRNA in response to mitogenic stimuli. Both T cells and large granular lymphocytes (LGL) possess stereospecific opiate receptor and opiate-neuroendocrine hormones, such as beta-endorphin, modulate the biological functions of these cells. Using radioligand autoradiography we have characterized IL 2 receptors in rat brain. The receptor for HIV was also observed in primate and human brain, approximately 57 kd, and mapping to areas distinct from IL 1 binding sites. We have studied the presence and distribution of cytokine mRNA in brain using in situ hybridization histochemistry. IL 1beta mRNA was detected in brain areas closely overlapping where IL 1 receptors are found. Only IL 18 mRNA, and not IL 1beta, was seen in rat and human brain. The processed mRNA was of a similar size as: seen in endotoxin-treated monocytes. The colony stimulating factor, IL 3, mRNA was also found in neurons in discrete areas of brain. The IL 3 mRNA is not associated with blood borne cells and shows a unique localization pattern when compared with IL 1beta mRNA.
