Abstract
The aim of this study was to characterize the action of the cytokine interleukin-6 (IL-6) on the chromaffin cells of the adrenal medulla. These cells are traditionally recognized for their role in the neuronally mediated ‘fight-flight’ response and also respond to a range of other stressful stimuli by secreting both catecholamines and neuropeptides. A relationship between the immune and stress systems is likely to be of physiological importance and the failure of this interaction may contribute to a number of pathologies. Bovine chromaffin cells were isolated, purified and cultured on collagen-coated wells. Cells were then washed with physiological buffer and incubated with IL-6 for 5-30 min. Western blotting was employed to detect the activation of specific signalling proteins, the blots scanned and comparisons made between basal and IL-6 stimulated samples. IL-6 significantly increased the phosphorylation of signal transducer and activator of transcription-3 and extracellular signal-related kinases 1/2 but not p-38 and Jun amino-terminal kinase. Immunohistochemistry showed that approximately 70% of chromaffin cells had phospho-STAT3 within their nuclei the distribution of phospho-ERK1/2 was predominantly within the cytoplasm of these cells. Cells were also incubated with IL-6 for 48 h and quantitative-PCR used to identify the gene changes in selected neuropeptides in these cells. IL-6 caused an increase in the mRNA of the following peptides: galanin, secretogranin II and pro-enkephalin.
The data obtained provides convincing evidence that the neuroendocrine chromaffin cells are responsive to IL-6 thus suggesting a potential pathway linking immune signals with the adrenal stress response.