Characterization of the LPS-induced inflammation of the adrenal gland in mice

Kanczkowski, Waldemar; Chatzigeorgiou, Antonios; Samus, Maryna; Tran, Nguyen; Zacharowski, Kai; Chavakis, Triantafyllos; Bornstein, Stefan R.

doi:10.1016/j.mce.2012.12.020

Cited by 36 publications

(25 citation statements)

References 32 publications

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“…Both LPS and CLP-OP induced sepsis are known to activate the HPA axis. We and others have shown that LPS administration acutely elevates ACTH and corticosterone levels [16,44]. In line with those studies, we have found that LPS strongly enriched genes involved in cholesterol metabolism and steroidogenesis pathways.…”

Section: Lps-enhanced Steroidogenesis and The Activation Of The Inflasupporting

confidence: 91%

“…In addition, we have also found and validated, strong upregulation of Csf2 and Csf3, also known and GM-CSF and G-CSF, as potent chemoattractants and growth factors that can alter the leukocyte recruitment and emergency hematopoiesis from the bone marrow [50]. The activation of those multiple chemokines in the adrenal gland may explain an increased infiltration of neutrophils and immature monocytes/macrophages after systemic LPS administration found in our previous studies [44,46]. Interestingly, the results of this RNA-seq analysis also validated our previous report showing LPSmediated Del-1 downregulation [16].…”

Section: Lps-enhanced Steroidogenesis and The Activation Of The Inflasupporting

confidence: 79%

“…Cxcl2, and proinflammatory mediators e.g. cyclooxygenases (Cox1 and Cox2) or prostaglandin synthase (mpges1) [44,45]. Furthermore, we have found that immune and hepatic but not adrenocortical inactivation of TLR-signaling resulted in decreased adrenal inflammation and corticosterone response after LPS administration [46].…”

Section: Lps-enhanced Steroidogenesis and The Activation Of The Inflamentioning

confidence: 77%

“…In the latter study, the ACTH-mediated PKA activation was proposed as a mechanism permitting differentiation of ZG cells into corticosterone producing adrenal cells [68]. During sepsis, strong activation of PKA, at least initially, is enhanced by high ACTH plasma levels [44]. Therefore, it is plausible that enhanced PKA activation may contribute to the Wnt pathway inhibition.…”

Section: Sepsis-induced Systemic Inflammation Is Associated With Redumentioning

confidence: 98%

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RNA-seq analysis of LPS-induced transcriptional changes and its possible implications for the adrenal gland dysregulation during sepsis

Chen

Singh

Schuster

et al. 2019

The Journal of Steroid Biochemistry and Molecular Biology

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Activation of the adrenal gland stress response is of utmost importance to survive sepsis. Experimental and clinical evidence exists demonstrating that adrenal gland often develops functional and structural damage due to sepsis with mechanisms remaining largely unknown. In the present study, we have used RNA Sequencing (RNA-Seq) technology to analyze changes in adrenal transcriptome elucidated by bacterial LPS. We aimed to find particularly alterations in genes that were previously not reported to be involved in the adrenal gland dysregulation in contexts of sepsis. Our results demonstrate that systemic administration of LPS significantly altered expression of 8458 genes as compared to saline injected animals. The subsequent quality and functional analysis of these gene signatures revealed that LPS-induced highly homogenous transcriptional response in total upregulating 4312 and downregulating 4146 genes. Furthermore, functional annotation analysis together with gene enrichment set analysis (GSEA) clearly demonstrated that adrenal response to LPS involved alterations in multiple pathways related to the inflammatory response along with previously unexplored activation of the hypoxia pathway. In addition, LPS strongly downregulated genes involved in the adrenal homeostasis, development, and regeneration. Those alterations were subsequently verified in clinically relevant cecal ligation and puncture (CLP)-induced sepsis model. Collectively, our study demonstrates that RNA-seq is a very useful method that can be applied to search for new unexplored pathways potentially involved in adrenal gland dysregulation during sepsis.

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Section: Lps-enhanced Steroidogenesis and The Activation Of The Inflasupporting

confidence: 91%

Section: Lps-enhanced Steroidogenesis and The Activation Of The Inflasupporting

confidence: 79%

Section: Lps-enhanced Steroidogenesis and The Activation Of The Inflamentioning

confidence: 77%

Section: Sepsis-induced Systemic Inflammation Is Associated With Redumentioning

confidence: 98%

See 2 more Smart Citations

RNA-seq analysis of LPS-induced transcriptional changes and its possible implications for the adrenal gland dysregulation during sepsis

Chen

Singh

Schuster

et al. 2019

The Journal of Steroid Biochemistry and Molecular Biology

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“…Expression of iNOS during inflammation is followed by overproduction of nitric oxide (NO) which is normally produced from the other isoforms of NOS [neural (nNOS) and endothelial (eNOS)] [39] . In adrenal cortex the normal level of NO was documented to be due to eNOS produced by its cells [40] . This could be supported in the present study by the presence of a basal level of NO in the control group despite the negative iNOS immunoreaction and its significant increase in LPS-group versus control.…”

Section: Discussionmentioning

confidence: 99%

Do microvesicles derived from adipose mesenchymal stem cells have a therapeutic potential on Escherichia coli lipopolysaccharides-induced sepsis in Zona fasciculata of adult male albino rats? A histological study

Omar

Aboulkhair

2018

Egyptian Journal of Histology

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Introduction: Sepsis is a major health problem with high mortality rate, despite advanced medications. Although hypothalamic-pituitary-adrenal (HPA) axis activation can control its destructive inflammatory reactions, adrenal insufficiency (AI) is commonly associated with it. Mesenchymal Stem Cell-Derived Microvesicles (MSCs-MVs) were proved to be as effective as their origin cells in tissue repair. Aim of the work: To study the effects of Escherichia coli-lipopolysaccharides (E. coli-LPS) induced sepsis on Zona fasciculata of adult male albino rats and probable therapeutic effects of adipose derived mesenchymal stem cells-microvesicles (ADMSCs-MVs). Materials and Methods: Forty-four adult male albino rats were divided into three groups; (I) the controls, (II) LPS and (III) MV. Sepsis was induced in LPS and MV-groups using E. coli-LPS. Four hours later, MV-group received single intravenous (IV) injection of PKH26 labelled ADMSCs-MVs. All animals were sacrificed 48 hours after ADMSCs-MVs administration. Tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nitric oxide (NO) levels were measured in adrenal homogenates of each group. Sections from all groups were subjected to H&E, besides, immunohistochemical stains for CD44, inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen (PCNA). Unstained sections of subgroup IC and MV-group were examined by fluorescent microscope. Mean number of CD44 and PCNA positive cells and mean area percent of iNOS immunoreaction were measured and data were statistically analyzed. Results: LPS-group showed non-survivors (24 hours after LPS-injection) and survivors with features of Zona fasciculata inflammatory damage, besides increased TNF-α and NO and decreased COX-2. The MV-group revealed marked increase in CD44 and PCNA, but significant decrease in iNOS immunoreactions. Additionally, ADMSCs-MV homing was detected in Zona fasciculata. Conclusion: LPS-induced sepsis caused marked Zona fasciculata inflammatory degeneration improved by ADMSCs-MVs single IV injection; mostly through transfer of proteins, mRNA, microRNA and/or organelles with reparative functions from ADMSCs to the injured tissues.

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Hepatic pannexin‐1 controls interleukin‐33 synthesis and release via the ATP‐P2X7 pathway with clinical implications for the resolution of hyperinflammation in sepsis

Vlachogiannis

Legaki

Chatzigeorgiou

2022

Clinical and Translational Dis

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Characterization of the LPS-induced inflammation of the adrenal gland in mice

Cited by 36 publications

References 32 publications

RNA-seq analysis of LPS-induced transcriptional changes and its possible implications for the adrenal gland dysregulation during sepsis

RNA-seq analysis of LPS-induced transcriptional changes and its possible implications for the adrenal gland dysregulation during sepsis

Do microvesicles derived from adipose mesenchymal stem cells have a therapeutic potential on Escherichia coli lipopolysaccharides-induced sepsis in Zona fasciculata of adult male albino rats? A histological study

Hepatic pannexin‐1 controls interleukin‐33 synthesis and release via the ATP‐P2X7 pathway with clinical implications for the resolution of hyperinflammation in sepsis

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