Opioid induced differential regulation of toll-like receptor 4

Abstract

With the growing recognition that toll-like receptor 4 (TLR4) interacts with opioids, this research aims to characterize these interactions in neuro-immune function. We have used the HEK-Blue-hTLR4 cell line to investigate opioid-induced TLR4 activity in the presence or absence of the TLR4 ligand lipopolysaccharide (LPS). Our results suggest that the opioids methadone, oxycodone, and buprenorphine significantly downregulate LPS-induced TLR4 activity while the effect of morphine was not significant. To further investigate the role of opioids and TLR4 in neuro-immune interaction, we used the human microglial cell line CHME-5. It was found that these cells robustly express TLR4 and the interleukin-1 receptor (IL-1R) but evidence regarding the human mu opioid receptor (hMOR) remains inconclusive. Additionally, morphine and methadone significantly upregulate TLR4 protein expression independently while methadone downregulates LPS-induced TLR4 protein expression. These findings have led to the conclusion that opioid-induced TLR4 activity and expression regulation may account in part for neuro-immune modulation by opioids.