TNFαAffects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium

Abstract

In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca+2 level ([Ca2+]i). We studied the effect of TNFα on the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue. Cultures were treated with TNFα, before and after the viscous load was changed. TNFα treatment produced a significantly larger decrease in CBF in cultures exposed to dextran. Furthermore, an increment in [Ca2+]i was observed, which was significantly larger after TNFα treatment. In conclusion, although TNFα has deleterious effects on ciliated cells in response to maintaining CBF after increasing viscous loading, it has a positive effect, since increasing [Ca2+]i may prevent the MCC collapse. These findings suggest that augmented levels of TNFα associated with an inflammatory response of the nasopharyngeal epithelium may have dual effects that contribute to maintaining the effectiveness of MCC in the upper airways.

microRNA–mRNA regulatory networks underlying chronic mucus hypersecretion in COPD

“…The movement of cilia is dependent, at least partially, on cyclic nucleotides and in particular on cAMPs [35]. In addition, active ion transport, such as that of Ca 2+ , Na + and Cl − , plays an important role in regulating mucus viscosity and mucociliary clearance [36,37], and both Ca 2+ and Na + can be transported through cyclic nucleotide-gated channels [38]. Notably, previous studies have suggested that neurohormonal signalling regulates cyclic guanosine monophosphate (cGMP) induced mucin secretion [39] and the expression of GDNF, the gene encoding for a neurotrophic factor involved in lung development, is associated with CMH in COPD [40].…”

Evaluation of Nasal Mucociliary Activity in Patients with Familial Mediterranean Fever

“…Proper mucus production and coordinated ciliary activity are required for effective mucociliary clearance. It has been shown in several studies that inflammatory cytokines are effective on NMC (15)(16)(17). In their study, Gonzalez et al (16) have revealed that TNF α, a proinflammatory cytokine, inhibits viscosity-related ciliary activity in human respiratory cultures.…”

“…It has been shown in several studies that inflammatory cytokines are effective on NMC (15)(16)(17). In their study, Gonzalez et al (16) have revealed that TNF α, a proinflammatory cytokine, inhibits viscosity-related ciliary activity in human respiratory cultures. Disruption of NMC increases the risk of infection in the upper and lower respiratory tract (9).…”