Keratinocyte chemoattractant (interleukin-8) regulation of sinonasal cilia function in a murine model.
Chronic rhinosinusitis is a multifactorial disease characterized by a local inflammatory response and impaired mucociliary clearance. Our prior work suggests that nonpolypoid inflammation can blunt ciliary dynamics. Thus, we set out to determine whether exogenously applied recombinant keratinocyte chemoattractant (KC), mouse homologue of interleukin-8 (IL-8), modulates ciliary function.
Murine primary sinonasal cultures were established in an air-liquid interface. Exogenous KC was administered to apical and basal surfaces at 500 pg/mL (n = 6) or 5 ng/mL (n = 3). Basal and stimulated cilia beat frequency (CBF) was recorded at 6, 12, 24, and 48 hours after exposure. Control groups were treated with buffered saline solution (n = 6). Cilia were mechanically stimulated with bursts of pressurized air (55 mmHg). CBF after prolonged KC exposure (96 hours) was also measured.
KC-treated cultures had significantly increased basal CBF at 24 hours and 48 hours. KC (500 pg/mL) yielded a 41.6% ± 9.5 increase in basal CBF (p < 0.001) at 24 hours, which persisted at 48 hours, 35.8% ± 10.2 (p < 0.05), while high-concentration KC (5 ng/mL) yielded a 50.2% ± 6.6 (p < 0.01) increase in basal CBF at 24 hours, which declined to 15.2% ± 5.2 (p < 0.01) at 48 hours. After 48 hours, the KC group demonstrated decreased response to mechanical stimulus vs control (500 pg/mL: p < 0.01, 5 ng/mL: p ≤ 0.04). With prolonged KC exposure (500 pg/mL) CBF declined: -25.5% ± 6.9 (p < .001) at 72 hours, and -19.6% ± 5.4 (p < 0.01) at 96 hours.
Our results demonstrate modulation of cilia function of murine sinonasal epithelial cells by the inflammatory cytokine KC, which acutely increases basal CBF while decreasing the response of cilia to mechanical stimulation. Prolonged KC exposure decreases basal CBF.
Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
SourceInternational forum of allergy & rhinology 2:1 pg 75-9
Dose-Response Relationship, Drug
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't