IL-13 regulates cilia loss and localization of cp110 in human nasal epithelium

Background: IL-13 is a key T helper cell (Th2) cytokine acts as an important mediator in nasal epithelial remodeling such as goblet cell hyperplasia and loss or dysfunction of ciliated cell. IL-13 contributes to airway remodeling by altering differentiation of airway basal/progenitor cells fate away from ciliated cells toward to goblet cells. The Centriolar coiled coil protein 110 (Cp110) is a critical regulator of cilia formation and is well known to suppress ciliogenesis, but its supportive role in ciliogenesis is not well understood Methods: We investigated IL-13 induced cilia loss in human nasal epithelial cells (hNECs) differentiation process using a pseudo-stratified epithelium in air-liquid interface (ALI) culture to determine how IL-13 alters ciliogenesis Results: We have confirmed that IL-13 reduced ciliated cells with impaired ciliary function by reducing of ciliary beating frequency and increased proportion of goblet cells on hNECs differentiation process in ALI. Immunofluorescence image of untreated hNECs showed that CP110 was a dotted pattern located in the nucleus of the cells at early stages (Day 0, 3 and 7) of ALI. From 14 to 21 day, Cp110 was found uniformly distributed at the base of ciliated cells and beating cilia can be found at the same time with positive staining of Fork head Box J1 (Foxj1) and βIV-tubulin. However, after IL-13 treatment, nuclear Cp110 was apparent and cilia were not found in most areas of lower ciliated cell densities at late stage of hNECs differentiation (Day 14 and 21). The mRNA levels of Cp110 and Foxj1 were decreased in the presence of IL-13 Conclusions: IL-13 may interfere Cp110 localizing to cilia–forming basal bodies to inhibit ciliated cell differentiation