Interleukin-6 is required for Neuregulin-1 induced HER2 signaling in lung epithelium.

Interleukin-6 is required for Neuregulin-1 induced HER2 signaling in lung epithelium.
Biochem Biophys Res Commun. 2019 Apr 15;:
Authors: Mishra R, Foster DG, Finigan JH, Kern JA
Abstract
A clear understanding of the mechanisms that regulate the alveolar epithelium's barrier is critical to develop new therapeutic strategies to mitigate lung injury. The HER2/HER3 receptor tyrosine kinase complex plays a central role in maintaining the alveolar-capillary barrier. This receptor complex is activated by its ligand, neuregulin-1 (NRG-1). Interleukin-6 (IL-6) is also known to induce HER2 signaling through HER2 transphosphorylation by the IL-6 receptor (IL-6R) complex (1). Due to this interaction, we hypothesized that NRG-1 and IL-6 cooperatively interacted to activate the HER2/HER3 complex. Studies were performed in cultured pulmonary epithelial cells measuring the HER2/IL-6/IL-6R/GP130 interaction and receptor activation by western blotting and confocal microscopy, IL-6 production by ELISA, and IL-6 inhibition using specific antibodies, small molecule inhibitors and shRNA. We found that IL-6 was required for NRG-1 induced activation of HER2 in pulmonary epithelial cells. IL-6 inhibition led to a decrease in NRG-1 induced HER2 activation. The IL-6R and GP130, a subunit of the IL-6R complex, were physically associated with HER2 and were required for NRG-1 induced HER2 activation. Inhibition of GP130, the β-subunit of the IL-6 receptor decrea...

Source: Biochemical and Biophysical Research communications - April 14, 2019 Category: Biochemistry Authors: Mishra R, Foster DG, Finigan JH, Kern JA Tags: Biochem Biophys Res Commun Source Type: research