RT Journal Article
T1 Alleviation of Microglial Activation Induced by p38 MAPK/MK2/PGE(2) Axis by Capsaicin: Potential Involvement of other than TRPV1 Mechanism/s
A1 Bhatia, Harsharan S.
A1 Roelofs, Nora
A1 Munoz, Eduardo
A1 Fiebich, Bernd L.
K1 Central-nervous-system
K1 Primary rat microglia
K1 Hippocampal slice cultures
K1 Prostaglandin-e synthase-1
AB Exaggerated inflammatory responses in microglia represent one of the major risk factors for various central nervous system's (CNS) associated pathologies. Release of excessive inflammatory mediators such as prostaglandins and cytokines are the hallmark of hyper-activated microglia. Here we have investigated the hitherto unknown effects of capsaicin (cap) - a transient receptor potential vanilloid 1 (TRPV1) agonist-in murine primary microglia, organotypic hippocampal slice cultures (OHSCs) and human primary monocytes. Results demonstrate that cap (0.1-25 mu M) significantly (p<0.05) inhibited the release of prostaglandin E2 (PGE2), 8-iso-PGF2α, and differentially regulated the levels of cytokines (TNF-α, IL-6 & IL-1β). Pharmacological blockade (via capsazepine & SB366791) and genetic deficiency of TRPV1 (TRPV1−/−) did not prevent cap-mediated suppression of PGE2 in activated microglia and OHSCs. Inhibition of PGE2 was partially dependent on the reduced levels of PGE2 synthesising enzymes, COX-2 and mPGES-1. To evaluate potential molecular targets, we discovered that cap significantly suppressed the activation of p38 MAPK and MAPKAPK2 (MK2). Altogether, we demonstrate that cap alleviates excessive inflammatory events by targeting the PGE2 pathway in in vitro and ex vivo immune cell models. These findings have broad relevance in understanding and paving new avenues for ongoing TRPV1 based drug therapies in neuroinflammatory-associated diseases.
PB Nature publishing group
SN 2045-2322
YR 2017
FD 2017-02-14
LK http://hdl.handle.net/10668/18905
UL http://hdl.handle.net/10668/18905
LA en
NO Bhatia HS, Roelofs N, Muñoz E, Fiebich BL. Alleviation of Microglial Activation Induced by p38 MAPK/MK2/PGE2 Axis by Capsaicin: Potential Involvement of other than TRPV1 Mechanism/s. Sci Rep. 2017 Mar 8;7(1):116
NO We thank Ulrike Götzinger-Berger and Brigitte Günter for their excellent technical assistance. Harsharan Singh Bhatia and Bernd L. Fiebich acknowledge Alzheimer Forschung Initiative e.V. (AFI) for providing pilot grant  (#13852) and standard grant (#10812), respectively. Alastair McGinness (University of Surrey, England) is greatly acknowledged for English corrections. We also thank Prof. Dr. Christoph Nissen for insightful discussion and for supervising MD thesis of Ms. Nora Roelofs. The article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding programme Open Access Publishing
DS RISalud
RD Apr 7, 2025