PMA Induces the MUC5AC Respiratory Mucin in Human Bronchial Epithelial Cells, via PKC, EGF/TGF-α, Ras/Raf, MEK, ERK and Sp1-dependent Mechanisms

Hewson, Christopher A.; Edbrooke, Mark R.; Johnston, Sebastian L.

doi:10.1016/j.jmb.2004.09.059

Cited by 164 publications

(194 citation statements)

References 34 publications

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“…In human bronchial epithelial cells, cigarette smoke-induced, as well as C5a-mediated, IL-8 expression [42] and TNF-ainduced intercellular adhesion molecule-1 expression [43] were blocked by calphostin C, and TNF-a-induced GM-CSF expression was inhibited by the pan-PKC blocker staurosporine [44]. In addition, HEWSON et al [45] reported that PMA-induced expression of the airway mucins MUC5B and MUC5AC by …”

Section: Discussionmentioning

confidence: 99%

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Slevogt

Maqami²,

Vardarowa³

et al. 2008

European Respiratory Journal

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Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells, M. catarrhalis induces release of the proinflammatory cytokine interleukin (IL)-8, which plays a pivotal role in orchestrating airway inflammation.The present study demonstrated that protein kinase (PK)C was activated by Moraxella infection and positively regulated M. catarrhalis-triggered nuclear factor (NF)-kB activation and subsequent IL-8 release. Activation of the PKC/NF-kB signalling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein A2. In addition, it was shown that specific isoforms of PKC play differential roles in the fine-tuning of the M. catarrhalis-induced NFkB-dependent gene expression through controlling il8 promoter activity. Inhibition of PKCa and e with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCh increased, the M. catarrhalis-induced IL-8 transcription and cytokine release.In conclusion, it was shown that Moraxella catarrhalis infection activates protein kinase C and its isoforms a, e and h, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Slevogt

Maqami²,

Vardarowa³

et al. 2008

European Respiratory Journal

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“…EGFR is expressed on airway epithelial cells, and in many cases its ligands, such as TGF-α and amphiregulin, are also present on the membrane in their inactive forms (55). Stimuli work by cleaving these ligands to their active forms, which then act in an autocrine or a paracrine manner to upregulate MUC5AC (18,73,74). As noted for NE, ROS are an important mechanism for stimulating MUC5AC.…”

Section: Transcriptional Activation Of Muc5ac Through Epidermal Growtmentioning

confidence: 98%

“…Likewise, environmental toxic agents such as cigarette smoke and ozone are important pathophysiological causes of diseases of COPD and emphysema, so their effects on airway epithelial cells and mucins have been explored. And finally, certain chemical agents such as phorbol esters that activate specific intracellular signaling cascades have been used to delineate specific signal transduction mechanisms that affect mucin gene expression (17)(18)(19). Despite the large number of heterogeneous mediators involved, patterns have emerged owing to the identification of a few specific signal transduction pathways and transcription mechanisms that are critical to mucin gene expression (Figure 1).…”

Section: Mucins Expressed In the Lungsmentioning

confidence: 99%

“…A CREB-responsive cis element on the MUC5AC promoter is present and is localized to the −776 to −929 region (68). Phorbol esters such as phorbol 12-myristate 13 acetate (PMA) can also activate MUC5AC expression through ERK pathways, but the downstream effects of PMA involve EGFR and Sp1 rather than CREB (18). A bacterial cytoplasmic protein from NTHI called P6 can activate MUC5AC expression.…”

Section: Muc5ac Expression Regulated By Map Kinasesmentioning

confidence: 99%

“…Signaling through EGFR (the ErbB1 receptor) has long been known to play an important role in modulating the expression of mucin genes (82,83). Many stimuli, including cigarette smoke, NE, phorbol esters, eosinophil products, bacterial products, and human airway trypsin-like protease, can upregulate MUC5AC through EGFR (18,73,74,(84)(85)(86). EGFR is expressed on airway epithelial cells, and in many cases its ligands, such as TGF-α and amphiregulin, are also present on the membrane in their inactive forms (55).…”

Section: Transcriptional Activation Of Muc5ac Through Epidermal Growtmentioning

confidence: 99%

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Regulation of Airway Mucin Gene Expression

Thai

Loukoianov

Wachi

et al. 2008

Annu. Rev. Physiol.

192

223

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Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.

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