RT Journal Article SR Electronic T1 Cigarette smoke upregulates IL-8/CXCL8 expression by augmenting mRNA stability via p38 MAPK/MK2 signalling in normal human pulmonary cells JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P1423 VO 40 IS Suppl 56 A1 Nadia Moretto A1 Giorgia Volpi A1 Manminder Kaur A1 Claudia Iadicicco A1 Serena Bertolini A1 Gessica Marchini A1 Dave Singh A1 Fabrizio Facchinetti YR 2012 UL http://erj.ersjournals.com/content/40/Suppl_56/P1423.abstract AB Interleukin-8 (IL-8/CXCL8) is an important neutrophil chemoattractant known to be elevated in the airways of cigarette smokers and in patients with chronic obstructive pulmonary disease (COPD), a syndrome associated with chronic cigarette smoking. We examined the acute effect of aqueous cigarette smoke extract (CSE) on IL-8 expression in normal human bronchial smooth muscle cells (HBSMC) and alveolar macrophages. CSE upregulates IL-8 mRNA levels in a concentration and time-dependent manner and such an effect was accompanied by IL-8 secretion into the extracellular medium. CSE-evoked elevation of IL-8 mRNA was mimicked by its component acrolein at concentrations (3-30µM) found in CSE. Both CSE and acrolein induced p38 mitogen-activated protein kinase (MAPK) phosphorylation which was accompanied by the phosphorylation of MAPK-activated kinase 2 (MK2), a known downstream substrate of the p38 MAPK. In both HBSMC and human alveolar macrophages, pharmacological inhibition of p38 MAPK or MK2 strongly accelerated the decay of IL-8 mRNA levels upon stimulation with CSE or acrolein and subsequent blockade of mRNA neosynthesis with actinomycin D. Conversely, pharmacological inhibition of extracellular-signal-regulated kinases 1/2 (ERK1/2) signalling did not affect mRNA stability but inhibited both CSE- and acrolein-induced steady-state levels of IL-8 mRNA, suggesting a transcriptional effect. In sum, p38 MAPK/MK2 signalling appear to be an important post-transcriptional mechanism underlying CSE-induced IL-8 mRNA upregulation.