Activation of the Heat Shock Response Attenuates the Interleukin 1β–Mediated Inhibition of the Amiloride-Sensitive Alveolar Epithelial Ion Transport

Howard, Marybeth; Roux, Jérémie; Iles, Karen E.; Miyazawa, Byron; Christiaans, Sarah C.; Anjum, Naseem; Dickinson, David B.; Goolaerts, Arnaud; Matthay, Michael A.; Pittet, Jean François

doi:10.1097/shk.0b013e31827e8ea3

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…The heat shock response has been classically defined as a highly conserved cellular defense mechanism. It has been well documented that pre-condition of heat shock restored alveolar fluid clearance in cultured alveolar type II cells and alveolar macrophages [35,36]. Heat shock proteins also had the similar effect on the animals with lung injury induced by sepsis [37] and ischemia-reperfusion [38].…”

Section: Discussionmentioning

confidence: 75%

Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor

Zhao

Zhang

Xiong

et al. 2016

Cell Physiol Biochem

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Background/Aims: Although it has been reported that somatostatin (SOM) upregulated the level of 90-kD heat shock protein (Hsp90), which participates in the inflammatory regulation by its client proteins, such as glucocorticoid receptor (GR), it remains unclear if it has a protective role against acute lung injury (ALI). Methods: ALI model was established by the injection of oleic acid (OA) into the tail vein of mice. Lung injury was assessed by histological analysis, lung water content and arterial blood gases. The levels of Hsp90 and GR, the binding capacity and the affinity of GR were examined. Results: It was showed that pretreatment with SOM significantly increased Hsp90 levels and alleviated lung injuries in OA-injected mice. Furthermore, SOM increased the GR expression and improved the affinity of the GR in animals with lung injury. However, little alteration was found in the maximum binding capacity of the GR in mice with or without SOM. Conclusion: The data indicate SOM exerts a protective effect by increasing Hsp90 abundant and further enhancing the affinity of the GR. The beneficial effects of SOM treatment provide a new strategy for modulation of GR efficiency and alleviation of acute lung injury.

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Section: Discussionmentioning

confidence: 75%

Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor

Zhao

Zhang

Xiong

et al. 2016

Cell Physiol Biochem

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“…For example, Il-1β signalling is dependent upon transforming growth factor beta-activated kinase 1 (TAK1) and IKK (25). Il-12, Il-23 and IFNγ signalling is dependent upon the JAK/STAT pathway where both JAK1, JAK2 (26), STAT1 (27) and STAT3 (28) have been shown to be client proteins of Hsp90. Moreover, Hsp90 inhibition has been shown to down-regulate phosphorylated STAT3 (29).…”

Section: Discussionmentioning

confidence: 99%

Debio 0932, A New Oral Hsp90 Inhibitor, Alleviates Psoriasis in a Xenograft Transplantation Model

Stenderup¹,

Rosada²,

Gavillet³

et al. 2014

Acta Derm Venerol

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Debio 0932 is a novel oral heat shock protein 90 (Hsp90) inhibitor developed for anti-cancer therapy. Surprising-ly, during the first clinical trial, one psoriasis patient experienced complete remission of his skin manifestation. However, a possible therapeutic utility of Hsp90 in psoriasis has not previously been reported. The objective of the present study was to explore the ability of Debio 0932 to alleviate psoriasis in a preclinical model. A psoriasis xenograft transplantation model was employed where skin from 5 psoriasis patients was transplanted onto immunodeficient mice (8 xenografts per donor). Debio 0932 was administered perorally daily for 3 weeks and resulted in significant clinical alleviation of psoriasis by day 11 and reduced epidermal thickness evaluated post-treatment. Alleviation of psoriasis in the psoriasis xenograft transplantation model, which may be due to Hsp90's involvement in signalling pathways that are up-regulated in psoriasis, substantiates a potential role of Debio 0932 in psoriasis treatment.

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“…When investigating patients with ALI, those who had an increased activation of the stress protein response (SPR) positively correlated with preserved alveolar clearance rates ( 114 ). Thus, activation of this SPR during immune-related injury may ameliorate effects of IL-1β, if used as a “preconditioning” agent ( 115 ).…”

Section: Cytokine-mediated Regulation Of Enacmentioning

confidence: 99%

Regulation of Lung Epithelial Sodium Channels by Cytokines and Chemokines

et al. 2017

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Acute lung injury leading to acute respiratory distress (ARDS) is a global health concern. ARDS patients have significant pulmonary inflammation leading to flooding of the pulmonary alveoli. This prevents normal gas exchange with consequent hypoxemia and causes mortality. A thin fluid layer in the alveoli is normal. The maintenance of this thin layer results from fluid movement out of the pulmonary capillaries into the alveolar interstitium driven by vascular hydrostatic pressure and then through alveolar tight junctions. This is then balanced by fluid reabsorption from the alveolar space mediated by transepithelial salt and water transport through alveolar cells. Reabsorption is a two-step process: first, sodium enters via sodium-permeable channels in the apical membranes of alveolar type 1 and 2 cells followed by active extrusion of sodium into the interstitium by the basolateral Na+, K+-ATPase. Anions follow the cationic charge gradient and water follows the salt-induced osmotic gradient. The proximate cause of alveolar flooding is the result of a failure to reabsorb sufficient salt and water or a failure of the tight junctions to prevent excessive movement of fluid from the interstitium to alveolar lumen. Cytokine- and chemokine-induced inflammation can have a particularly profound effect on lung sodium transport since they can alter both ion channel and barrier function. Cytokines and chemokines affect alveolar amiloride-sensitive epithelial sodium channels (ENaCs), which play a crucial role in sodium transport and fluid reabsorption in the lung. This review discusses the regulation of ENaC via local and systemic cytokines during inflammatory disease and the effect on lung fluid balance.

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Activation of the Heat Shock Response Attenuates the Interleukin 1β–Mediated Inhibition of the Amiloride-Sensitive Alveolar Epithelial Ion Transport

Cited by 7 publications

References 38 publications

Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor

Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor

Debio 0932, A New Oral Hsp90 Inhibitor, Alleviates Psoriasis in a Xenograft Transplantation Model

Regulation of Lung Epithelial Sodium Channels by Cytokines and Chemokines

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