Ceramide in Cystic Fibrosis: A Potential New Target for Therapeutic Intervention

Table 1

Summary of studies on ceramide in cystic fibrosis.

Author	Model used	Method of analysis	Results
Studies reporting low levels of ceramide in CF
Vilela et al. [83]	Human tracheal epithelial cells	HPLC	Ceramide was found to increase more in cells lacking CFTR than those with functioning CFTR following fenretinide treatment
Guilbault et al. [8]	Plasma from CF patients, and CF mice (B6. Cftr^tm1unc); Plasma from CF patients and; CF mice (B6. Cftr^tm1unc)	HPLC/MS (13 species of ceramide and 2 dihydroceramide species); TLC followed by ELISA (antibody clone 15B4)	↓ in C14, C20 : 1, C22, C22 : 1, C24, DHC16 in patients; ↓in total ceramide levels in patients and mice (plasma and CF related organs).; Improvement in bacterial clearance when ceramide is ↑ after fenretinide treatment in CF mice following intratracheal infection with P. aeruginosa; Correlation between ELISA and MS techniques (𝑃=.002, 𝑟=0.541, 𝑟^2=0.293).
Saeed et al. [78]	CF mice (B6. Cftr^tm1unc)	TLC followed by ELISA (antibody clone 15B4)	↓in total ceramide levels in mice (plasma and CF related organs).
Guilbault et al. [4]	Plasma from; CF patients; CF mice (B6. Cftr^tm1unc)	TLC followed by ELISA (antibody 15B4)	↓ in total ceramide levels in patients and CF mice, correlated with defects in fatty acids
Yu et al. [84]	Bronchial epithelial cells (S9 and IB3-1); Cftr^tm1unc- Tg^(FABPCFTR)	HPLC/MS	Ceramide levels are ↓ in cells lacking CFTR compared to control cells during infection.
Noe et al. [85]	Human microvascular endothelial cells	LC/MS (11 species of ceramide and 5 dihydroceramide species)	↑ in ceramide in response to H2O2 in cells where CFTR is expressed.; When CFTR is inhibited, there is no ceramide response.
Studies reporting high levels of ceramide in CF
Teichgräber et al. [22]	CF mice (Cftr^tm1unc- Tg^(FABPCFTR) and B6.129P2(CF/3)- Cftr^TgH(neoim)Hgu); Human nasal epithelial cells; Explanted human lung tissue	Liquid scintillation counting; Immunofluorescence (antibody clone S58-9)	↑ in total ceramide levels in CF mice and human cells; Blocking aSMase causes a ↓ in ceramide; Improvement in bacterial clearance in CF mice when aSMase is inhibited and ceramide levels ↓
Becker et al. [86]	CF mice (Cftr^tm1unc- Tg^(FABPCFTR) and B6.129P2(CF/3)-Cftr^TgH(neoim)Hgu)	Immunofluorescence (antibody clone S58-9) DAG kinase assay LC/MS (3 species of ceramide)	↑ in total ceramide levels (data represented sum of C16, C18, and C20); Inhibition of aSMase results in ↓ in ceramide and in reduction in susceptibility to intranasal infection with P. aeruginosa
Ulrich et al. [87]	Explanted human lung tissue	Immunofluorescence (antibody clone S58-9)	↑ in ceramide in CF lungs
Zhang et al. [88]	Alveolar mouse macrophages	DAG kinase assay Immunofluorescence (antibody clone S58-9)	↑ in total ceramide in CF cells; ↑ in ceramide following infection in WT cells, not in CF cells
Brodlie et al. [21]	Explanted human lung tissue	Immunofluorescence (antibody clones S58-9 and 15B4); HPLC/MS (4 species of ceramide)	↑ in total ceramide (observed with staining of antibodies); ↑ in C16, C18, C20. No change in C22.
Study reporting high and low levels of specific ceramide species in CF
Hamai et al. [89]	16HBE14o(-) cells with or lacking CFTR expression	TLC and liquid scintillation counting	↑ in levels of DHC16, C22, C24, C26; ↓ in levels of C18, C18 : 1