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NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance

Institute of NeuroImmune Pharmacology, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA
Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA
Author to whom correspondence should be addressed.
Academic Editor: Donna Gruol
Brain Sci. 2017, 7(2), 14;
Received: 22 June 2016 / Revised: 11 January 2017 / Accepted: 16 January 2017 / Published: 6 February 2017
(This article belongs to the Special Issue Advances in Neuroimmunology)
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance. Morphine tolerance was elicited using the 2 + 4 morphine-pelleting protocol. On Day 1, the rats were pelleted subcutaneously with 2 pellets of morphine (75 mg/pellet) or a placebo; on Days 2 and 4 pellets were given. On Day 5, the animals were randomly assigned to receive either 250 µg/kg LPS or saline (i.p.). The expression of 84 inflammasome related genes in the rat brain was examined using a Ploymerase Chain Reaction (PCR) array. In response to LPS, there was a significant increase in the expression of the pro-inflammatory cytokine/chemokine genes interleukin-1 beta (Il-1β), interleukin-6 (Il-6), C-C motif chemokine ligand 2 (Ccl2), C-C motif chemokine ligand 7 (Ccl7), C-X-C motif chemokine ligand 1 (Cxcl1), and C-X-C motif chemokine ligand 3 (Cxcl3) and a significant decrease in the anti-inflammatory NLRP12 gene in both morphine-tolerant and placebo-control rats compared to saline-treated rats, although the changes were greater in the placebo-control animals. The Library of Integrated Network-Based Cellular Signatures’ (LINCS) connectivity map was used to analyze the list of affected genes to identify potential targets associated with the interactions of LPS and morphine tolerance. Our data indicate that, in the morphine tolerant state, the expression of NLRP12 and its related genes is altered in response to LPS and that the Vacuolar protein-sorting-associated protein 28 (VPS28), which is involved in the transport and sorting of proteins into sub-cellular vesicles, may be the key regulator of these alterations. View Full-Text
Keywords: morphine tolerance; NLRP12 inflammasome; LPS morphine tolerance; NLRP12 inflammasome; LPS
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Chang, S.L.; Huang, W.; Mao, X.; Sarkar, S. NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance. Brain Sci. 2017, 7, 14.

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