Abstract：
BACKGROUND:We hypothesized that the peculiar mixed interleukin-4 (IL-4/Th2) and interferon gamma INF-γ (INF-γ/Th1) inflammatory milieu found in the airways of patients with aspirin-exacerbated respiratory disease (AERD) is responsible for the altered regulation of the IL-1β/IL-1RI-/EP2/COX-2 autocrine loop also found in these patients. The objective of the study is to demonstrate that IL-4 and INF-γ cytokines, are capable of inducing in healthy nasal mucosa (NM) the dysregulation of the autocrine loop of COX reported in AERD. SUBJECTS AND METHODS:Fibroblasts were obtained from NM (n = 8). To evaluate the role of IL-4 and IFN-γ on the autocrine loop, fibroblasts were incubated with or without IL-1β, in the presence or absence of IL-4 and/or IFN-γ for 48 h. After this period, the expression of EP2, EP3, EP4, IL-1RI, COX-2 and mPGES-1 was measured by Western blot. RESULTS:Stimulation of fibroblasts with IL-1β significantly increased the expression of EP2, but had no effects on EP3 and EP4 expression Incubation with IL-4 or IFN-γ alone was not able to modify the expression of any of the components of the autocrine loop. In contrast, co-treatment with IL-4 and IFN-γ was able to significantly inhibit IL-1β-induced EP2, IL-1RI, COX-2 and mPGES-1. CONCLUSION:These results suggest that the mixed Th1/Th2 inflammatory pattern found in the airways of AERD patients might be responsible for the altered regulation of the COX pathway also reported in these asthma patients.
journal_name
Respir Medjournal_title
Respiratory medicineauthors
Machado-Carvalho L,Roca-Ferrer J,Picado Cdoi
10.1016/j.rmed.2019.03.008subject
Has Abstractpub_date
2019-04-01 00:00:00pages
136-140eissn
0954-6111issn
1532-3064pii
S0954-6111(19)30083-6journal_volume
150pub_type
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