Mycoplasma infection transforms normal lung cells and induces bone morphogenetic protein 2 expression by post‐transcriptional mechanisms

Bone morphogenetic protein 2 (BMP2) is an essential growth factor and morphogen, whose pattern and level of expression profoundly influences development and physiology. We present the novel finding that mycoplasma infection induces BMP2 RNA production in six cell lines of diverse types (mesenchymal, epithelial, and myeloid). Mycoplasma infection triggered the expression of mature secreted BMP2 protein in BEAS-2B cells (immortalized human bronchial epithelial cells), which normally do not express BMP2, and further increased BMP2 production in A549 cells (lung adenocarcinoma cells). Indeed, mycoplasma is as strong an experimental inducer as inflammatory cytokines and retinoic acid. Second, we showed that post-transcriptional mechanisms including regulation of RNA stability, rather than transcriptional mechanisms, contributed to the increased BMP2 expression in mycoplasma-infected cells. Furthermore, a novel G-rich oligonucleotide, AS1411 that binds the post-transcriptional regulator nucleolin induced BMP2 exclusively in infected cells. Finally, BMP2 stimulated proliferation in BEAS-2B cells transformed by chronic mycoplasma infection, as demonstrated by treatment with Noggin, a BMP2 antagonist. These findings have important implications regarding the effects of mycoplasma on BMP2-regulated processes, including cell proliferation, differentiation, and apoptosis.