Increased glucocorticoid receptor expression in sepsis is related to heat shock proteins, cytokines, and cortisol and is associated with increased mortality

Abstract Context.—A precise role for the innate immune system in psoriasis remains to be determined. Surface receptors, including Toll-like receptors (TLRs) that recognize bacterial ligands and CD91, which recognizes heat shock proteins (HSPs), are implicated in both innate and adaptive immunity. Objective.—Since skin is exposed to various exogenous stimuli, which can provoke or exacerbate psoriasis, we characterized expression and function of TLRs, CD91, and HSPs in normal and psoriatic skin. Design.—A variety of skin-derived cells and blood-derived cells were analyzed both in vivo and in vitro; samples were obtained from 24 different individuals for innate immune-related receptor expression and function. By comparing and contrasting individuals with healthy skin and psoriatic patients, several specific differences were identified. Results.—Immunohistochemistry-based expression profiling revealed TLR1 expression in epidermal dendritic cells (DCs) and dermal dendritic cells (DDCs) in normal skin, as well as in pre-psoriatic skin and psoriatic plaques, with enhanced basal layer keratinocyte (KC) expression in pre-psoriatic and psoriatic plaques compared with normal skin; TLR2 expression primarily by DDCs; and TLR4 expression by epidermal DCs and DDCs, with mid-epidermal-layer KCs displaying cell surface staining. No TLR9 or CD14 was detected on DCs or KCs, although psoriatic plaques contained CD14-positive macrophages. Analysis of psoriatic epidermis revealed HSPs 27, 60, and 70. Keratinocytes were CD91 negative, but CD91 was expressed by fibroblasts and DDCs in normal and pre-psoriatic skin, with prominent accumulation of CD91-positive DDCs in psoriatic plaques. Cultured KCs revealed no surface expression of TLR2, TLR4, TLR9, or CD91. Exposure of fibroblasts, but not KCs, to lipopolysaccharide or HSPs triggered nuclear factor (NF)-κB activation. Heat shock proteins did induce maturation of blood-derived DCs accompanied by increased interleukin-12 production and enhanced antigen-presenting function. Conclusions.—These data demonstrate distinctive patterns of innate immune-related receptors by specific subsets of cells in normal and psoriatic skin, suggesting functional roles for HSPs and DCs in psoriasis.

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Gender-related differences in the effects of antidepressant imipramine on glucocorticoid receptor binding properties and association with heat shock proteins in the rat liver and kidney

European Journal of Pharmacology ◽

10.1016/j.ejphar.2009.02.038 ◽

2009 ◽

Vol 608 (1-3) ◽

pp. 7-13 ◽

Cited By ~ 6

Author(s):

Ivana Elaković ◽

Jelena Brkljačić ◽

Gordana Matić

Keyword(s):

Heat Shock ◽

Heat Shock Proteins ◽

Glucocorticoid Receptor ◽

Rat Liver ◽

Receptor Binding ◽

Binding Properties ◽

Antidepressant Imipramine ◽

Liver And Kidney ◽

Shock Proteins

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Bronchial thermoplasty in asthma: an exploratory histopathological evaluation in distinct asthma endotypes/phenotypes

Respiratory Research ◽

10.1186/s12931-021-01774-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Eleni Papakonstantinou ◽

Triantafyllia Koletsa ◽

Liang Zhou ◽

Lei Fang ◽

Michael Roth ◽

...

Keyword(s):

Smooth Muscle ◽

Heat Shock ◽

Epithelial Cells ◽

Heat Shock Proteins ◽

Heat Shock Protein ◽

Glucocorticoid Receptor ◽

Airway Smooth Muscle ◽

Heat Shock Protein 90 ◽

Bronchial Thermoplasty ◽

Shock Proteins

Abstract Background Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes. Methods Endobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining. Results In all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034). In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes. Conclusions Bronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.

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Melatonin and thermal stress regulate differential expression of heat shock proteins and melatonin receptors in spleen of mice

Indian Journal of Pharmaceutical and Biological Research ◽

10.30750/ijpbr.3.1.7 ◽

2015 ◽

Vol 3 (01) ◽

pp. 36-47 ◽

Cited By ~ 1

Author(s):

Samik Acharjee ◽

Shiv Shankar Singh

Keyword(s):

Thermal Stress ◽

Heat Shock ◽

Heat Shock Proteins ◽

Receptor Expression ◽

Melatonin Receptors ◽

Hsp70 Expression ◽

Immune Functions ◽

Experimental Conditions ◽

Shock Proteins ◽

Thermally Stressed

Cellular defence by expression of heat shock proteins (Hsps) against stress stimulation is the most universal phenomenon in stress physiology. Melatonin is well known as an anti-stress molecule possessing hypothermic effects. It protects cells and tissues in stressed conditions. Individually, Hsp70 and melatonin shows its functional ability in stressed organisms as well as in immune functions. The aim of the present study was to determine the interaction of melatonin receptors (MT1/MT2) in exogenous melatonin modulated expression of heat shock proteins (Hsp70/Hsc70) in spleen of thermally stressed male mice. Results of the study showed thermal stress significantly increased the Hsp70/Hsc70 and melatonin receptor MT2 expression in spleen of mice. The administration of melatonin significantly increased Hsp70 expression, but decreased Hsc70 expression. Both MT1/MT2 receptor expressions increased after melatonin treatment, whereas thermal stress to melatonin treated mice showed decrease in MT1/MT2 receptor expression than the only melatonin treated mice. MT2 receptor is responding in all experimental conditions corresponding to changes in Hsp70 protein expression. Therefore, the present study might suggest that MT2 receptor is interacting in coordination of melatonin mediated heat shock proteins expression in mice spleen after thermally stressed conditions.

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