Impact assessment of repeated exposure of organotypic 3D bronchial and nasal tissue culture models to whole cigarette smoke.
Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers.
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Diana
D
Kuehn
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Shoaib
S
Majeed
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Emmanuel
E
Guedj
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Remi
R
Dulize
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Karine
K
Baumer
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Anita
A
Iskandar
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.; Stephanie.Boue@pmi.com.
Stephanie
S
Boue
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Florian
F
Martin
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Radina
R
Kostadinova
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Carole
C
Mathis
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Nikolai V
NV
Ivanov
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Stefan
S
Frentzel
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Julia
J
Hoeng
Biological Systems Research, Philip Morris International R&D, Philip Morris Products S.A.
Manuel C
MC
Peitsch
D001980:Bronchi / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008168:Lung / Q000473:pathology*; D009297:Nasal Mucosa / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D046509:Tissue Culture Techniques / Q000379:methods*
D012906:Smoke; D003577:Cytochrome P-450 Enzyme System