ABSTRACTELUCIDATING MECHANISMS OF NEUROGENIC INFLAMMATION IN THE MOUSE OLFACTORY EPITHELIUMByTania Riyan Iqbal Inflammation in the nervous system is linked to neurological disorders and neurodegenerative disease, and inflammation can be initiated by exposure to pollutants. The olfactory epithelium (OE) is directly exposed to the environment and prone to damage; however, the mechanisms of inflammation in the OE are not well understood. As a precursor to understanding chronic inflammation, I study modulation of acute inflammation in the mouse OE. Neurogenic inflammation is a form of acute inflammation caused by the release of pro-inflammatory peptides from nerves. Neurogenic inflammation can be initiated via local depolarization or axonal reflexes rather than cellular damage or infiltration of pathogens as in classical inflammation. Here, I tested the hypothesis that irritants initiate neurogenic inflammation in the mouse OE through activation of the trigeminal nerve and neuropeptide release. The pattern of immunoreactivity of irritant-sensing channels transient receptor potential -vanilloid 1 (TRPV1) and -ankyrin 1 (TRPA1) in OE tissue suggests a role in activation of the trigeminal fiber and secondary chemosensory cells (i.e., microvillous cells) in the OE. The pro-inflammatory neuropeptide substance P was released from tissue upon exposure to TRPV1 and TRPA1 agonists capsaicin and cinnamaldehyde, causing plasma extravasation, a hallmark of inflammation. Substance P treatment of OE tissue induced the release of cytokines tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, presumably from macrophages, a major source of inflammatory mediators. The receptor for substance P, neurokinin-1, was found throughout the OE, including on macrophages and non-neuronal cells within the OE, implicating these cells in neurogenic inflammation of the OE. Macrophages were identified in the OE and found at increased levels in degenerating tissue and after exogenous application of substance P. This study identifies the trigeminal nerve, TRP channels, and macrophages as key factors in the initiation of the inflammatory response, i.e., the release of pro-inflammatory cytokines, and suggests that environmental irritation may initiate acute inflammation in the OE. Although acute inflammation can be beneficial in recovery from damage, it is important to understand the underlying mechanisms involved, as progression to chronic inflammation can lead to disease states.
Read
