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Absence of C/EBPα may cause bronchial smooth muscle proliferation in asthma
  1. N M Rahman
  1. Specialist Registrar, Respiratory Medicine, Horton Hospital, Banbury, Oxon, UK; naj_rahmanyahoo.co.uk

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Proliferation of bronchial smooth muscle (BSM) cells occurs in the airways of asthmatic patients. Glucocorticoids exert antiproliferative effects via CCAAT/enhancer binding protein α (C/EBPα), an antiproliferative transcription factor. This paper studies signalling pathways in BSM cell proliferation from 20 asthmatic and 26 non-asthmatic subjects (lung cancer/CF/emphysema).

A series of elegant experiments (using immunoblotting/electrophoresis) first established that, in response to glucocorticoid, asthmatic and non-asthmatic BSM cells display similar glucocorticoid receptor (GR) characteristics, similar anti-inflammatory effects (interleukin (IL)-6 suppression), and a similar reduction in IL-6 suppression with a GR inhibitor. However, whereas glucocorticoid significantly suppresses cell proliferation in control BSM cells (by 24–28%), no such suppression is seen in asthmatic BSM cells. None of the asthmatic cell lines expressed the C/EBPα transcription factor whereas all controls did (tissue specific to BSM). Transfection of asthmatic cells with a C/EBPα expression vector significantly slowed (and allowed steroids to suppress) proliferation.

The authors conclude that asthmatic BSM cell proliferation results from absence of C/EBPα, which also explains the lack of steroid suppression. Steroid treatment suppresses IL-6 production in both groups, therefore demonstrating two distinct signalling pathways: anti-inflammatory (cytokine mediated) and antiproliferative (transcription factor mediated).

Why asthmatic BSM cells lack C/EBPα remains unclear (previous steroid use and treatment length were often unknown, perhaps influencing in vitro response) and whether CF or emphysema subjects can be used as controls is debatable. The implication that steroids do not suppress BSM proliferation in asthma is clearly important and the demonstration of two distinct signalling pathways merits further investigation.

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