Toll interacting protein protects bronchial epithelial cells from bleomycin‐induced apoptosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by altered epithelial cell phenotypes, which are associated with myofibroblast accumulation in the lung. Atypical alveolar epithelial cells in IPF express molecular markers of airway epithelium. Polymorphisms within and around Toll interacting protein (TOLLIP) are associated with the susceptibility to IPF and mortality. However, the functional role of TOLLIP in IPF is unknown. Using lung tissues from IPF and control subjects, we showed that expression of TOLLIP gene in the lung parenchyma is globally lower in IPF compared to controls. Lung cells expressing significant levels of TOLLIP include macrophages, alveolar type II, and basal cells. TOLLIP protein expression is lower in the parenchyma of IPF lungs but is expressed in the atypical epithelial cells of the distal fibrotic regions. Using overexpression and silencing approaches, we demonstrate that TOLLIP protects cells from bleomycin-induced apoptosis using primary | 9885 LI et aL.

Potential clinical utility of MUC5B und TOLLIP single nucleotide polymorphisms (SNPs) in the management of patients with IPF

“…A study investigating TOLLIP expression in lung tissue of IPF patients revealed that the TOLLIP expressing cells were macrophages, alveolar type II, and basal cells. A mechanistic assay using basal cells showed that TOLLIP was able to reduce mitochondrial ROS accumulation following bleomycin-induced mitochondrial damage of basal cells (31). All these data together corroborate the hypothesis of a protective effect of TOLLIP in several cell populations against oxidative damage and brosis.…”

“…The importance of TOLLIP in IPF is emphasized by the relationship between biological impact and potential disease outcome. Besides the well-known role in in ammation and autoimmunity by enhancing signaling pathways associated with IL-1β, TNF-a, IFN-b, IL-13, toll-like receptor (TLR) (29) and autophagy (30), a recent study revealed that TOLLIP protects bronchial epithelial cells from bleomycininduced apoptosis (31). A study investigating TOLLIP expression in lung tissue of IPF patients revealed that the TOLLIP expressing cells were macrophages, alveolar type II, and basal cells.…”

Potential Clinical Utility of MUC5B und TOLLIP Single Nucleotide Polymorphisms (SNPs) in the Management of Patients with IPF

“…A study investigating TOLLIP expression in lung tissue of IPF patients revealed that the TOLLIP expressing cells were macrophages, alveolar type II, and basal cells. A mechanistic assay using basal cells showed that TOLLIP was able to reduce mitochondrial ROS accumulation following bleomycin-induced mitochondrial damage of basal cells (30). All these data together corroborate the hypothesis of a protective effect of TOLLIP in several cell populations against oxidative damage and brosis.…”

“…The importance of TOLLIP in IPF is emphasized by the relationship between biological impact and potential disease outcome. Besides the well-known role in in ammation and autoimmunity by enhancing signaling pathways associated with IL-1β, TNF-a, IFN-b, IL-13, toll-like receptor (TLR) (28) and autophagy (29), a recent study revealed that TOLLIP protects bronchial epithelial cells from bleomycininduced apoptosis (30). A study investigating TOLLIP expression in lung tissue of IPF patients revealed that the TOLLIP expressing cells were macrophages, alveolar type II, and basal cells.…”

Genetic Risk Factors for Idiopathic Pulmonary Fibrosis: Insights into Immunopathogenesis

“…20,21 Regardless, TOLLIP has been shown to suppress TLR activation, particularly TLR2 and TLR4, by inhibiting IL-1 receptor-associated kinase (IRAK) phosphorylation. [77][78][79][80] Both TLR2 and TLR4 activation occur in response to many different microbial signals and have been shown to be elevated in IPF epithelia, possibly due to chronic exposure to pathogenic microbes. 81 Reduced TOLLIP expression has been shown to increase proinflammatory cytokine (IL-6 and TNF) production by macrophages after TLR stimulation.…”