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Airway smooth muscle cells (ASMCs) participate in tissue remodeling characteristic of airway inflammatory diseases like asthma. Inflammation and hypoxia pathways are often interconnected and the regulatory subunit of the hypoxia inducible factor, HIF‐1α, has been recently shown to be induced by cytokines. Here we investigate the effect of individual or combined treatment of ASMCs with the inflammatory mediator TNFα and/or hypoxia on the expression of HIF‐1α, HIF‐1 targets and inflammation markers. TNFα enhances HIF‐1α protein and mRNA levels, under both normoxia and hypoxia. TNFα‐mediated induction of HIF‐1α gene transcription is repressed by inhibition of the NF‐κB pathway. Despite the up‐regulation of HIF‐1α protein, the transcription of HIF‐1 target genes remains low in the presence of TNFα at normoxia and is even reduced at hypoxia. We show that the reduction in HIF‐1 transcriptional …