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Rapid co‐release of interleukin 1β and caspase 1 in spinal cord inflammation
Author(s) -
Clark Anna K.,
D'Aquisto Fulvio,
Gentry Clive,
Marchand Fabien,
McMahon Stephen B.,
Malcangio Marzia
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04126.x
Subject(s) - microglia , spinal cord , inflammation , mapk/erk pathway , p38 mitogen activated protein kinases , biology , pharmacology , microbiology and biotechnology , immunology , neuroscience , kinase
Mounting evidence supports the hypothesis that pro‐inflammatory cytokines secreted by astrocytes and microglia modulate nociceptive function in the injured CNS and following peripheral nerve damage. Here we examine the involvement of interleukin‐1β (IL‐1β) and microglia activation in nociceptive processing in rat models of spinal cord inflammation. Following application of lipopolysaccharide (LPS) to an ex vivo dorsal horn slice preparation, we observed rapid secretion of IL‐1β which was prevented by inhibition of glial cell metabolism and by inhibitors of either p38 mitogen‐activated protein kinase (MAPK) or caspase 1. LPS superfusion also induced rapid secretion of active caspase 1 and apoptosis‐associated speck‐like protein containing a caspase recruitment domain from the isolated dorsal horn. Extensive microglial cell activation in the dorsal horn, as determined by immunoreactivity for phosphorylated p38 MAPK, was found to correlate with the occurrence of IL‐1β secretion. In behavioural studies, intrathecal injection of LPS in the lumbar spinal cord produced mechanical hyperalgesia in the rat hind‐paws which was attenuated by concomitant injections of a p38 MAPK inhibitor, a caspase 1 inhibitor or the rat recombinant interleukin 1 receptor antagonist. These data suggest a critical role for the cytokine IL‐1β and caspase 1 rapidly released by activated microglia in enhancing nociceptive transmission in spinal cord inflammation.