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Norepinephrine differentially modulates the innate inflammatory response provoked by amyloid-β peptide via action at β-adrenoceptors and activation of cAMP/PKA pathway in human THP-1 macrophages

Title
Norepinephrine differentially modulates the innate inflammatory response provoked by amyloid-β peptide via action at β-adrenoceptors and activation of cAMP/PKA pathway in human THP-1 macrophages
Authors
Yang J.H.Lee E.O.Kim S.E.Suh Y.-H.Chong Y.H.
Ewha Authors
정영해
SCOPUS Author ID
정영해scopus
Issue Date
2012
Journal Title
Experimental Neurology
ISSN
0014-4886JCR Link
Citation
vol. 236, no. 2, pp. 199 - 206
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Evidence indicates that norepinephrine (NE) has antiinflammatory activities and plays a neuroprotective role where inflammatory events contribute to Alzheimer's disease pathology. Here, we evaluated the effects of NE on amyloid beta 1-42 (Aβ1-42)-induced cytotoxicity and proinflammatory cytokine/chemokine secretion, and determined the mechanisms through which NE exerts its actions in human THP-1 macrophages. NE clearly reduced the Aβ1-42-mediated production of the proinflammatory chemokine, monocytic chemotactic protein-1 (MCP-1/CCL2). In contrast to its ability to reduce MCP-1 secretion, NE enhanced the amounts of the proinflammatory cytokine interleukin (IL)-1β secreted from Aβ1-42 treated cells. NE significantly reduced the Aβ1-42-induced cytotoxicity in situations where it contributed to the increased IL-1β and decreased MCP-1 during Aβ1-42 stimulation. The ability of NE to differentially modulate the Aβ1-42-induced immune responses was mediated by β-adrenoceptors, as the aforementioned effects were replicated by the β-adrenoceptor agonist, isoproterenol, and blocked by the β-adrenoceptor antagonist, dl-propranolol. Of note, the NE effects on Aβ1-42-induced responses were mimicked by dbcAMP and forskolin, but significantly blocked by H89, an inhibitor of PKA. Moreover, NE abolished Aβ1-42-mediated decline of CREB phosphorylation. Overall, NE suppresses Aβ1-42-mediated cytotoxicity and MCP-1 secretion, but enhances Aβ-mediated IL-1β secretion through action at β-adrenoceptors, accompanied by activation of cAMP/PKA pathway and CREB in human microglia-like THP-1 cells. © 2012 Elsevier Inc..
DOI
10.1016/j.expneurol.2012.05.008
Appears in Collections:
의과대학 > 의학과 > Journal papers
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