NPY and NPY receptors in airway structural and inflammatory cells in allergic asthma.
OBJECTIVE
Neuropeptide Y (NPY) level is elevated in allergic asthmatic airways and activation of NPY receptor-1 (NPY-Y1) on antigen-presenting cells (APCs) is essential for T cell priming. Paradoxically, NPY-Y1 modulates hyper-responsiveness in T cells, suggesting a bimodal role for NPY in APCs and T cells. Therefore, determination of the temporal and spatial expression pattern of NPY and its receptors in asthmatic airways is essential to further understand the role of NPY in allergic asthma.


METHODS
Lungs were isolated from control and acute and chronic stages of OVA-sensitized and challenged mice (OVA). Stains, including H&E, PAS, and trichrome, were used to determine the severity of lung pathology. The expression patterns of NPY and NPY-Y receptors in the airways were determined using ELISA and immunofluorescence. Cytokine levels in the BALF were also measured.


RESULTS
NPY levels were undetectable in the BALF of control mice, but significantly increased in the OVA group at day 80. Levels of IL-4, TGF-β1 and TGF-β2, significantly increased and peaked on day 45 and decreased on day 80 in the OVA group, exhibiting an inverse correlation with NPY levels. NPY expression was localized to macrophage-like cells in the peri-bronchial and peri-vascular areas in the lung tissue. NPY-Y1 and -Y5 receptors were constitutively expressed by both structural and inflammatory cells in the lung tissue.


CONCLUSIONS
NPY produced by activated macrophage-like cells may be involved in regulating cytokine production and cellular activities of immune cells in asthma. However, it remains unclear whether such an increase in NPY is a defensive/compensatory mechanism to modulate the effects of inflammatory cytokines.
Center of Clinical and Translational Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
Toluwalope O
TO
Makinde
Robert
R
Steininger
Devendra K
DK
Agrawal
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004789:Enzyme Activation; D007249:Inflammation / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009478:Neuropeptide Y / Q000378:metabolism*; D010047:Ovalbumin; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D012137:Respiratory System; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D015847:Interleukin-4; D010047:Ovalbumin