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Olfactory loss in chronic rhinosinusitis is associated with neuronal activation of c‐Jun N‐terminal kinase
Author(s) -
Victores Andrew J.,
Chen Mengfei,
Smith Amy,
Lane Andrew P.
Publication year - 2018
Publication title -
international forum of allergy and rhinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.503
H-Index - 46
eISSN - 2042-6984
pISSN - 2042-6976
DOI - 10.1002/alr.22053
Subject(s) - inflammation , medicine , neuroinflammation , c jun , kinase , neuroprotection , olfactory system , signal transduction , microglia , apoptosis , neuroscience , microbiology and biotechnology , immunology , biology , transcription factor , biochemistry , gene
Background Olfactory inflammation in chronic rhinosinusitis (CRS) is associated with cytokines that may result in the death of olfactory sensory neurons. The principal signaling molecules involved in the apoptotic pathway are c‐Jun N‐terminal kinases (JNK). Although the JNK pathway has emerged as a key player in programmed cell death in neuroinflammation, its specific role in CRS‐associated olfactory loss has not been thoroughly investigated. Methods JNK activation was studied in human tissue samples from 9 control and 11 CRS patients by immunohistochemical staining for phosphorylated c‐Jun. A mouse model of inducible olfactory cytokine expression was used to experimentally control inflammation and assess JNK activation over time. Results In patients with CRS, activation of c‐Jun is significantly increased relative to non‐CRS control subjects, and there is an associated loss of sensory neurons. In the olfactory inflammation mouse model, prolonged induction of inflammation results in elevation of c‐Jun expression and neuronal apoptosis. Conclusion Activation of neuronal JNK is a feature of chronic olfactory inflammation that is associated with neuronal apoptosis. Given that inhibition of JNK activity is neuroprotective in other settings, antagonism of this pathway may have therapeutic potential in the management of inflammatory olfactory loss or other disorders linked to olfactory neuronal apoptosis.