RETRACTED: REDOX regulation of IL-13 signaling in intestinal epithelial cells: Usage of alternate pathways mediates distinct gene expression patterns

Mandal, Debasmita; Fu, Pingfu; Levine, Alan D.

doi:10.1016/j.cellsig.2010.05.017

Cited by 51 publications

(47 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-13 is known to increase reactive oxygen species (ROS) (6)(7)(8), and the airways of asthma patients and allergen-challenged mice contain high levels of ROS that appear to contribute to asthma (9)(10)(11)(12)(13). ROS are known to be important in TGF-b signaling through a number of mechanisms.…”

mentioning

confidence: 99%

Mitochondrial-Targeted Antioxidant Therapy Decreases Transforming Growth Factor-β–Mediated Collagen Production in a Murine Asthma Model

Jaffer¹,

Carter

Sanders³

et al. 2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Asthma is a disease of acute and chronic inflammation in which cytokines play a critical role in orchestrating the allergic inflammatory response. IL-13 and transforming growth factor (TGF)-b promote fibrotic airway remodeling, a major contributor to disease severity. Improved understanding is needed, because current therapies are inadequate for suppressing development of airway fibrosis. IL-13 is known to stimulate respiratory epithelial cells to produce TGF-b, but the mechanism through which this occurs is unknown. Here, we tested the hypothesis that reactive oxygen species (ROS) are a critical signaling intermediary between IL-13 or allergen stimulation and TGF-b-dependent airway remodeling. We used cultured human bronchial epithelial cells and an in vivo mouse model of allergic asthma to map a pathway where allergens enhanced mitochondrial ROS, which is an essential upstream signal for TGF-b activation and enhanced collagen production and deposition in airway fibroblasts. We show that mitochondria in airway epithelium are an essential source of ROS that activate TGF-b expression and activity. TGF-b from airway epithelium stimulates collagen expression in fibroblasts, contributing to an early fibrotic response to allergen exposure in cultured human airway cells and in ovalbumin-challenged mice. Treatment with the mitochondrialtargeted antioxidant, (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mitoTEMPO), significantly attenuated mitochondrial ROS, TGF-b, and collagen deposition in OVA-challenged mice and in cultured human epithelial cells. Our findings suggest that mitochondria are a critical source of ROS for promoting TGF-b activity that contributes to airway remodeling in allergic asthma. Mitochondrial-targeted antioxidants may be a novel approach for future asthma therapies.

show abstract

mentioning

confidence: 99%

Mitochondrial-Targeted Antioxidant Therapy Decreases Transforming Growth Factor-β–Mediated Collagen Production in a Murine Asthma Model

Jaffer¹,

Carter

Sanders³

et al. 2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…In addition, pSTAT6 expression also appears to increase in the pathogenesis of asthma. All of these indicate that pSTAT6 and GATA3 have different pathological functions (Mandal et al, 2010;Poritz et al, 2010;McCallister et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6

Zhou

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT.To study the role of boswellic acid in reducing asthma phenotype severity and the relationship between the expression of pSTAT6 and GATA3, thirty-six mice were randomly divided into normal control group, asthma group, and boswellic acid group (treatment group). The asthma model was established through an intraperitoneal injection of sensitization liquid (0.15 mL aluminum hydroxide gel at 88.67 mg/ mL and 0.05 mg ovalbumin). pSTAT6 and GATA3 expression levels in peripheral blood were detected by reverse transcription-polymerase chain reaction and Western blot analysis. pSTAT6 and GATA3 gene expressions in the asthmatic group were significantly higher than in the normal control group; they were markedly lower in the treatment group than the asthma group, and there was no significant difference when compared with the normal control group. The pSTAT6 expressions in the asthma, control and treatment groups were 2.256 ± 0.125, 0.524 ± 0.210, and 0.897 ± 0.134 at gray level, respectively. The GATA3 expressions in the asthma, control, and treatment groups were 3.521 X. Zhou et al. 7464©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 7463-7468 (2015) ± 0.631, 0.435 ± 0.136, and 0.743 ± 0.149 at gray level, respectively. pSTAT6 and GATA3 expression levels were similar in the treatment and control groups. GATA3 expression had a positive correlation with pSTAT6 expression. Boswellic acid may improve asthma symptoms by inhibiting pSTAT6 expression, which consequently reduces GATA3 expression.

show abstract

“…28 IL13 stimulates ROS production in both intestinal and airway epithelial cell lines. 18,19,39 We evaluated the influence of IL13 on intracellular ROS levels in the hTEC model (Fig. 2E).…”

Section: Il13 Induces Muc5ac Secretion In Human Tracheobronchial Epitmentioning

confidence: 99%

IL13 activates autophagy to regulate secretion in airway epithelial cells

et al. 2016

View full text Add to dashboard Cite

Cytokine modulation of autophagy is increasingly recognized in disease pathogenesis, and current concepts suggest that type 1 cytokines activate autophagy, whereas type 2 cytokines are inhibitory. However, this paradigm derives primarily from studies of immune cells and is poorly characterized in tissue cells, including sentinel epithelial cells that regulate the immune response. In particular, the type 2 cytokine IL13 (interleukin 13) drives the formation of airway goblet cells that secrete excess mucus as a characteristic feature of airway disease, but whether this process is influenced by autophagy was undefined. Here we use a mouse model of airway disease in which IL33 (interleukin 33) stimulation leads to IL13-dependent formation of airway goblet cells as tracked by levels of mucin MUC5AC (mucin 5AC, oligomeric mucus/gel forming), and we show that these cells manifest a block in mucus secretion in autophagy gene Atg16l1-deficient mice compared to wild-type control mice. Similarly, primary-culture human tracheal epithelial cells treated with IL13 to stimulate mucus formation also exhibit a block in MUC5AC secretion in cells depleted of autophagy gene ATG5 (autophagy-related 5) or ATG14 (autophagyrelated 14) compared to nondepleted control cells. Our findings indicate that autophagy is essential for airway mucus secretion in a type 2, IL13-dependent immune disease process and thereby provide a novel therapeutic strategy for attenuating airway obstruction in hypersecretory inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis lung disease. Taken together, these observations suggest that the regulation of autophagy by Th2 cytokines is cell-context dependent.

show abstract

RETRACTED: REDOX regulation of IL-13 signaling in intestinal epithelial cells: Usage of alternate pathways mediates distinct gene expression patterns

Cited by 51 publications

References 48 publications

Mitochondrial-Targeted Antioxidant Therapy Decreases Transforming Growth Factor-β–Mediated Collagen Production in a Murine Asthma Model

Mitochondrial-Targeted Antioxidant Therapy Decreases Transforming Growth Factor-β–Mediated Collagen Production in a Murine Asthma Model

Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6

IL13 activates autophagy to regulate secretion in airway epithelial cells

Contact Info

Product

Resources

About