Premium
8’‐glycinil β ‐ carboline inhibits nitric oxide formation but not NF‐kB‐mediated inflammatory responses in macrophages (LB614)
Author(s) -
Grodzki Ana,
Gorin Fredric,
Lein Pamela
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb614
Subject(s) - nitric oxide , neuropathic pain , nitric oxide synthase , pharmacology , hyperalgesia , microglia , inflammation , chemistry , proinflammatory cytokine , nf κb , nociception , p38 mitogen activated protein kinases , mapk/erk pathway , medicine , kinase , biochemistry , immunology , receptor , organic chemistry
Neuropathic pain arising secondarily from an acute nerve injury is frequently associated with a protracted inflammatory response. While multiple inflammatory molecules, signaling pathways and neurochemical alterations contribute to chronic neuropathic pain, an essential role for nitric oxide generated by peripheral macrophages and microglia in the dorsal root ganglia and spinal cord has been reported. Specifically, the non‐selective nitric oxide synthase (NOS) inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) was reported to reduce thermal hyperalgesia in inflammatory pain models and selective blockers for constitutive NOS and inducible NOS have been shown to reduce inflammatory response and neuropathic pain. Here, as part of a screen for novel therapeutics for neuropathic pain, we studied the effects of a novel hydrophilic 8’‐glycinyl 6‐chloro beta carboline (8’‐Gly carb) on nitric oxide formation and NF‐kB activation in macrophages. Our data show that 8’‐Gly carb inhibits constitutive and inducible nitric oxide formation and interferes with NF‐kB‐mediated reporter. However, 8’‐Gly carb does not affect NF‐kB p65 subunit translocation to the nuclei or expression of pro‐inflammatory cytokines TNF and IL‐1β . Moreover, 8’‐Gly carb does not inhibit Erk 1/2 or P38 MAP kinase activity. Since 8’‐Gly carb significantly inhibits constitutive and inducible nitric oxide formation without interfering with downstream effects of NF‐kB, 8’‐Gly carb holds promise as an agent that might be used to reduce neuropathic pain in the face of chronic inflammation.Grant Funding Source : Supported by NIH/NIEHS ES017592