title: MAPK- and PKC/CREB-dependent induction of interleukin-11 by the environmental contaminant formaldehyde in human bronchial epithelial cells.
abstract: Formaldehyde (FA) is a volatile organic compound (VOC), considered as a major indoor air pollutant and suspected to favor the development of inflammatory lung diseases. The present study was aimed at identifying cytokines/chemokines targeted by FA in human lung cells. This VOC was demonstrated to up-regulate interleukin-11 (IL-11) mRNA and secretion levels in a dose-dependent manner in cultured lung epithelial BEAS-2B cells. It concomitantly induced mRNA expression of transforming growth factor (TGF)-β1, a fibrogenic marker regulated by IL-11. FA was also found to trigger an early phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinases (MAPKs) in BEAS-2B cells, whose inhibition by ERK and p38 MAPK chemical inhibitors (U0126 and SB203580, respectively) counteracted FA-mediated induction of IL-11. In addition, FA increased phosphorylation of cAMP response element binding protein (CREB) and the use of small-interfering RNA targeting CREB demonstrated that this transcription factor was required for the up-regulation of IL-11 by FA. Implication of protein kinase C (PKC) in FA-induced IL-11 expression was moreover demonstrated by using RO-31-8220, a PKC inhibitor. We finally showed using SB203580 and RO-31-8220 that phosphorylation of CREB and CREB-promoter activity induced by FA are under the control of both p38 MAPK and PKC. Taken together, the results showed that FA uses different pathways to induce IL-11 expression in lung BEAS-2B cells. IL-11, well-known to contribute to lung inflammatory diseases, appears thus as a molecular target of FA, which could be involved in putative deleterious inflammatory and fibrogenic pulmonary effects of this VOC.
authors.affiliation: EA4427-SeRAIC, IFR140, Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, Rennes, France. valerie.lecureur@univ-rennes1.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Lecureur
authors.forename: Matthieu
authors.initials: M
authors.lastname: Arzel
authors.forename: Sarah
authors.initials: S
authors.lastname: Ameziane
authors.forename: Noémie
authors.initials: N
authors.lastname: Houlbert
authors.forename: Marc
authors.initials: M
authors.lastname: Le Vee
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D004785:Environmental Pollutants / Q000633:toxicity*; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004785:Environmental Pollutants; D017370:Interleukin-11; D011994:Recombinant Proteins; D005557:Formaldehyde; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases