Matches in SemOpenAlex for { <https://semopenalex.org/work/W2063498634> ?p ?o ?g. }
- W2063498634 endingPage "560" @default.
- W2063498634 startingPage "554" @default.
- W2063498634 abstract "The spinal release of prostaglandins (PGs), nitric oxide (NO), and cytokines has been implicated in spinal nociceptive processing. Microglia represent a possible cell of origin for these proexcitatory mediators. Spinal microglia possess Toll-like receptor 4 (TLR4) and neurokinin 1 (NK1) receptors, and both receptors play a significant role in peripheral nerve injury- and inflammation-induced spinal sensitization. Accordingly, we examined the properties of the cascades activated by the respective targets, which led to the release of PGE(2) and an increase in nitrite (NO(2)(-)) (a marker of NO) from cultured rat spinal microglia.Spinal microglia isolated from Sprague-Dawley neonatal rats were cultured with lipopolysaccharide (LPS) or substance P (SP) alone, with LPS in combination with SP, and with LPS in the presence of each inhibitor of cyclooxygenase (COX), NO synthase 2 (NOS2) or p38 mitogen-activated protein kinase (p38), or minocycline for 24 hours and 48 hours. Concentrations of PGE(2) and NO(2)(-) in culture supernatants were measured using an enzyme immunoassay and a colorimetric assay, respectively.Application of LPS (a TLR4 ligand, 0.1 to 10 ng/mL) to cultured microglia produced a dose- and time-dependent increase in PGE(2) and NO(2)(-) production, whereas no effects were observed after incubation with SP (an NK1 agonist, up to 10(-5) M) alone or in combination with LPS. Antagonist studies with SC-560 (COX-1 inhibitor) and SC-236 (COX-2 inhibitor) showed that LPS-induced PGE(2) release was generated from both COX-1 and COX-2. LPS-induced NO release was suppressed by 1400W, an inhibitor of NOS2. Minocycline, an agent blocking microglial activation, and SB203580, an inhibitor of p38, both attenuated the LPS-induced PGE(2) and NO release. The 1400W, at the doses that suppressed NO release, also blocked increased PGE(2) release.Our findings suggest that (a) activation of spinal microglia via TLR4 but not NK1 receptors produces PGE(2) and NO release from these cells; (b) the evoked PGE(2) release is generated by both COX-1 and COX-2, and (c) the COX-PGE(2) pathway is regulated by p38 and NOS2. Taken together with our previous in vivo work, the current findings emphasize that p38 in spinal microglia is a key player in regulating production of pronociceptive molecules, such as PGE(2) and NO." @default.
- W2063498634 created "2016-06-24" @default.
- W2063498634 creator A5000276702 @default.
- W2063498634 creator A5039522795 @default.
- W2063498634 creator A5042389999 @default.
- W2063498634 creator A5050647760 @default.
- W2063498634 creator A5070089176 @default.
- W2063498634 creator A5084944304 @default.
- W2063498634 date "2010-08-01" @default.
- W2063498634 modified "2023-10-14" @default.
- W2063498634 title "Release of Prostaglandin E2 and Nitric Oxide from Spinal Microglia Is Dependent on Activation of p38 Mitogen-Activated Protein Kinase" @default.
- W2063498634 cites W1510794723 @default.
- W2063498634 cites W1612226764 @default.
- W2063498634 cites W1651539757 @default.
- W2063498634 cites W17682570 @default.
- W2063498634 cites W177250915 @default.
- W2063498634 cites W1829029306 @default.
- W2063498634 cites W1920952343 @default.
- W2063498634 cites W1953774514 @default.
- W2063498634 cites W1980341424 @default.
- W2063498634 cites W1981310258 @default.
- W2063498634 cites W1984025105 @default.
- W2063498634 cites W1984252894 @default.
- W2063498634 cites W1985214132 @default.
- W2063498634 cites W1993418316 @default.
- W2063498634 cites W1994768747 @default.
- W2063498634 cites W1997450735 @default.
- W2063498634 cites W2001751920 @default.
- W2063498634 cites W2015951393 @default.
- W2063498634 cites W2018789478 @default.
- W2063498634 cites W2019128864 @default.
- W2063498634 cites W2028057402 @default.
- W2063498634 cites W2031565182 @default.
- W2063498634 cites W2036436547 @default.
- W2063498634 cites W2040768738 @default.
- W2063498634 cites W2042968258 @default.
- W2063498634 cites W2050822001 @default.
- W2063498634 cites W2052840755 @default.
- W2063498634 cites W2053758653 @default.
- W2063498634 cites W2055297480 @default.
- W2063498634 cites W2056262623 @default.
- W2063498634 cites W2056945159 @default.
- W2063498634 cites W2065451295 @default.
- W2063498634 cites W2067931227 @default.
- W2063498634 cites W2070312747 @default.
- W2063498634 cites W2076473797 @default.
- W2063498634 cites W2081939036 @default.
- W2063498634 cites W2084709188 @default.
- W2063498634 cites W2091430115 @default.
- W2063498634 cites W2100040118 @default.
- W2063498634 cites W2107508545 @default.
- W2063498634 cites W2113617025 @default.
- W2063498634 cites W2114688563 @default.
- W2063498634 cites W2116500181 @default.
- W2063498634 cites W2119747146 @default.
- W2063498634 cites W2121761530 @default.
- W2063498634 cites W2124667416 @default.
- W2063498634 cites W2140193821 @default.
- W2063498634 cites W2149714164 @default.
- W2063498634 cites W2152087455 @default.
- W2063498634 cites W2153465192 @default.
- W2063498634 cites W2153989172 @default.
- W2063498634 cites W2158230836 @default.
- W2063498634 cites W2170019750 @default.
- W2063498634 cites W2316274675 @default.
- W2063498634 cites W2399849325 @default.
- W2063498634 cites W3158470188 @default.
- W2063498634 cites W4230173358 @default.
- W2063498634 doi "https://doi.org/10.1213/ane.0b013e3181e3a2a2" @default.
- W2063498634 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20610553" @default.
- W2063498634 hasPublicationYear "2010" @default.
- W2063498634 type Work @default.
- W2063498634 sameAs 2063498634 @default.
- W2063498634 citedByCount "45" @default.
- W2063498634 countsByYear W20634986342012 @default.
- W2063498634 countsByYear W20634986342013 @default.
- W2063498634 countsByYear W20634986342014 @default.
- W2063498634 countsByYear W20634986342015 @default.
- W2063498634 countsByYear W20634986342016 @default.
- W2063498634 countsByYear W20634986342017 @default.
- W2063498634 countsByYear W20634986342018 @default.
- W2063498634 countsByYear W20634986342019 @default.
- W2063498634 countsByYear W20634986342020 @default.
- W2063498634 countsByYear W20634986342021 @default.
- W2063498634 countsByYear W20634986342022 @default.
- W2063498634 crossrefType "journal-article" @default.
- W2063498634 hasAuthorship W2063498634A5000276702 @default.
- W2063498634 hasAuthorship W2063498634A5039522795 @default.
- W2063498634 hasAuthorship W2063498634A5042389999 @default.
- W2063498634 hasAuthorship W2063498634A5050647760 @default.
- W2063498634 hasAuthorship W2063498634A5070089176 @default.
- W2063498634 hasAuthorship W2063498634A5084944304 @default.
- W2063498634 hasBestOaLocation W20634986341 @default.
- W2063498634 hasConcept C126322002 @default.
- W2063498634 hasConcept C134018914 @default.
- W2063498634 hasConcept C170493617 @default.
- W2063498634 hasConcept C184235292 @default.
- W2063498634 hasConcept C2776070231 @default.