Inflammatory mediators increase the expression of nociceptin/orphanin FQ in rat astrocytes in culture

✍ Scribed by Beata Buzas; J. Rosenberger; Kee-Won Kim; Brian M. Cox

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 212 KB
• Volume: 39
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.10106

✦ Synopsis

Abstract

In the central nervous system, glial cells play an important role in inflammatory and immune responses, and opioid peptides have been identified as essential mediators between the nervous and the immune systems. We report the profound upregulation of the opioid‐related nociceptin/orphanin FQ (N/OFQ) by inflammatory mediators in astrocytes. The bacterial endotoxin, lipopolysaccharide (LPS), and the proinflammatory cytokines, interleukin‐β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), induced levels of N/OFQ mRNA and immunoreactivity. HPLC analysis of the immunoreactivity in astrocyte extracts revealed that a large molecular weight precursor for N/OFQ is being synthesized and released in response to LPS and astrocytes appear to lack the enzymes required to process the precursor protein. Western blot analysis showed that LPS treatment elicited the activation of ERK 1/2 and p38 MAP kinases. Blockade of the p38 or the ERK MAP kinase pathways prevented the LPS‐induced increase in N/OFQ mRNA levels indicating a role for these cascades in the regulation of N/OFQ genes in response to LPS. Regulation of N/OFQ gene expression by ERK and p38 activation may be mediated through the transcription factor CREB. We observed CREB phosphorylation in response to LPS, which was also prevented by SB202190 and PD98059. The NFκB pathway also appears to be involved in the induction of N/OFQ transcription by LPS, since NFκB inhibitors antagonized the effect of LPS on N/OFQ expression. Regulation of N/OFQ by inflammatory mediators in astrocytes may suggest a role for N/OFQ in neural–glial communication and in inflammatory responses in certain neuropathophysiological conditions. GLIA 39:237–246, 2002. Published 2002 Wiley‐Liss, Inc.