Abstract
Asthma is characterized by chronic bronchial inflammation and is a highly heterogeneous disease strongly influenced by both specific and non-specific exogenous factors. The present study was performed to assess the effect of nasal allergen provocation tests and methacholine provocation tests on the mRNA co-expression patterns of genes (SMAD1/3/6/7, MPK1/3 and TGFB1/3) involved in SMAD and non-SMAD TGF-β signaling pathways in patients with asthma. Reverse transcription-quantitative PCR was performed on blood samples taken pre-provocation and 1 h post-provocation to assess gene expression changes. Of the 59 patients studied, allergen provocations were administered to 27 patients and methacholine provocations to 32 patients. Correlations between expression levels of studied genes were found to be influenced markedly by the challenge administered, challenge test result and time elapsed since challenge. Importantly, increases in expression levels for four gene pairs (MAPK1-SMAD3, MAPK3-SMAD3, SMAD1-SMAD3 and SMAD3-TGFB1) were found to correlate significantly with asthma occurrence in the allergen provocation cohort, but not in the methacholine provocation cohort. The present study allows us to draw the conclusion that both intranasal allergen and bronchial methacholine challenges influence mRNA co-expression patterns of the SMAD1/3/6/7, MPK1/3 and TGFB1/3 genes.