CFTR Is a Negative Regulator of NFκB Mediated Innate Immune Response (original) (raw)
Figure 7
Hypothetical model of CFTR mediated NFκB signaling and innate immune response.
The lack of functional CFTR on the cell surface or inhibition of lipid raft localization by methyl-β-cyclodextrin (CD) de-regulates pro-inflammatory signaling via TNFα-IL1β-TLR pathways resulting in an overactive innate immune response, chronic NFκB mediated inflammation, and lung destruction. Our data suggest that localization of functional CFTR at the cell surface in cholesterol rich lipid rafts serves as a negative regulator of NFκB signaling. We propose that restoration of an optimal amount of functional CFTR on the cell surface can control chronic inflammatory pathophysiology of CF lung disease by not only restoring the chloride efflux function but by also regulating the chronic NFκB mediated inflammatory signaling.