IL-1 β dysregulates cGMP signaling in the newborn lung.

IL-1β dysregulates cGMP signaling in the newborn lung.
Am J Physiol Lung Cell Mol Physiol. 2020 May 06;:
Authors: Zhong Y, Bry K, Roberts JD
Abstract
Cyclic guanosine monophosphate (cGMP) signaling is an important regulator of newborn lung function and development. Although cGMP signaling is decreased in many models of newborn lung injury, the mechanisms are poorly understood. We determined how IL-1β regulates the expression of the α1-subunit of soluble guanylate cyclase (sGCα1), a prime effector of pulmonary cGMP signaling. Physiologic levels of IL-1β were discovered to rapidly decrease sGCα1 mRNA expression in a human fetal lung fibroblast cell line (IMR-90 cells) and protein levels in primary mouse pup lung fibroblasts. This sGCα1 expression inhibition appeared to be at a transcriptional level; IL-1β treatment did not alter sGCα1 mRNA stability although it reduced sGCα1 promoter activity. TGFβ-activated kinase 1 (TAK1) was determined to be required for IL-1β's regulation of sGCα1 expression; TAK1 knockdown protected sGCα1 mRNA expression in IL-1β-treated IMR-90 cells. Moreover, heterologously expressed TAK1 was sufficient to decrease sGCα1 mRNA levels in those cells. Nuclear factor-kappaB (NF-κB) signaling played a critical role in the IL-1β-TAK1-sGCα1 regulatory pathway; chromatin immunoprecipitation studies demonstrated enhanced activated NF-kB subunit (RelA) binding to the sGCα1 promoter after IL-1β treatme...

Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - May 5, 2020 Category: Cytology Authors: Zhong Y, Bry K, Roberts JD Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research