IFI16 Facilitates Inflammatory Endothelial Pathophenotypes Observed Among Individuals With PAH, Study Finds

Pulmonology Advisor (1/2, Jacobs) reports, “Interferon gamma inducible protein 16 (IFI16), which is an important part of the inflammatory signaling cascade, facilitates the inflammatory endothelial pathophenotypes observed among individuals with pulmonary arterial hypertension (PAH), according to findings from a mechanistic study.” Researchers, “using both PAH patient samples and experimental PAH models...observed a distinct elevation in IFI16 mRNA levels in human pulmonary artery endothelial cells (PAECs). Correspondingly, IFI16 knockdown inhibits apoptosis, increases proliferation, and decreases proinflammatory markers in PAECs.” The researchers “observed that inflammatory stimulus of PAECs with interleukin-1β was able to upregulate IFI16 expression, thus generating proinflammatory cytokine upregulation and cellular apoptosis.” The investigators “also showed that the stability of IFI16 mRNA is regulated through inflammation-generated posttranscriptional modification by Wilms’ tumor-associated protein.” The findings were published in the American Journal of Physiology-Lung Cellular and Molecular Physiology.