title: PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.
abstract: A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC) is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B) cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu), and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute University Health Network, Toronto, Ontario, Canada.
authors.forename: Hyunhee
authors.initials: H
authors.lastname: Kim
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zamel
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Bai
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D046228:Microarray Analysis; D016328:NF-kappa B / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C