Regulation of the β-endorphin precursor proopiomelanocortin in lymphocytes in a rat model of inflammatory pain

Abstract

Our previous studies have shown that monocytes/macrophages, granulocytes, and lymphocytes release opioid peptides in the presence of different releasing factors at the site of peripheral tissue injury or inflammation and thereby contribute to opioid-mediated reduction of pain. We are interested in the regulation of β-endorphin and its precursor proopiomelanocortin (POMC) at the transcriptional and posttranslational level in lymphocytes, as such cells play a role in chronic inflammation. We hypothesized that (i) POMC gene expression in the lymph node draining inflamed tissue is up-regulated in inflammation, and (ii) that the precursor is cleaved by the prohormone convertases (PC)1 and PC2 similar to neuroendocrine cells in the pituitary gland. We found elevated POMC gene expression and β-endorphin levels in cells of lymph nodes draining inflamed tissue, as assessed by qPCR and radioimmunoassay. Our PCR and immunocytochemistry data show that PC1 mRNA and protein expression, respectively, are induced after induction of inflammation. PC2 required no stimulation and was detectable using PCR and immunocytochemistry, both, in cells from nai¨ve and activated lymph nodes. Our findings indicate that β-endorphin synthesis in lymphocytes may depend on the presence of PC1/3, while PC2 alone does not seem to be sufficient. Functional experiments are necessary to verify the specific roles of these enzymes for POMC processing in cells of the immune system.