scholarly journals Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2376
Author(s):  
Kimberly Wellman ◽  
Rui Fu ◽  
Amber Baldwin ◽  
Juilee Rege ◽  
Elisabeth Murphy ◽  
...  
Keyword(s):  
Primary Cultures ◽  
Specific Aspect ◽  
Multiple Time ◽  
Primary Cells ◽  
Response Dynamics ◽  
Hormone Production ◽  
Adrenocortical Cells ◽  
Transcriptomic Response ◽  
Gene Expression Response ◽  
H295r Cells

Adrenal steroid hormone production is a dynamic process stimulated by adrenocorticotropic hormone (ACTH) and angiotensin II (AngII). These ligands initialize a rapid and robust gene expression response required for steroidogenesis. Here, we compare the predominant human immortalized cell line model, H295R cell, with primary cultures of adult adrenocortical cells derived from human kidney donors. We performed temporally resolved RNA-seq on primary cells stimulated with either ACTH or AngII at multiple time points. The magnitude of the expression dynamics elicited by ACTH was greater than AngII in primary cells. This is likely due to the larger population of adrenocortical cells that are responsive to ACTH. The dynamics of stimulus-induced expression in H295R cells are mostly recapitulated in primary cells. However, there are some expression responses in primary cells absent in H295R cells. These data are a resource for the endocrine community and will help researchers determine whether H295R is an appropriate model for the specific aspect of steroidogenesis that they are studying.

scholarly journals Interleukin-8 Synthesis, Regulation, and Steroidogenic Role in H295R Human Adrenocortical Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 891-898 ◽  
Author(s):  
Damian G. Romero ◽  
Gaston R. Vergara ◽  
Zheng Zhu ◽  
Gina S. Covington ◽  
Maria W. Plonczynski ◽  
...  
Keyword(s):  
Immune System ◽  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Interferon Γ ◽  
Cell Culture Supernatant ◽  
Adrenocortical Cells ◽  
Adrenal Cells ◽  
Endothelin 1 ◽  
H295r Cells ◽  
First Time

The adrenal gland secretes several cytokines, and cytokines modulate steroid secretion by this gland. In this study, a survey of cytokine production by H295R human adrenocortical cells demonstrated that these cells secreted IL-2, IL-4, IL-8, IL-10, IL-13, and TNFα but not IL-5, IL-12, or interferon-γ. IL-8 was the IL secreted at higher concentration. IL-8 secretion, its regulation, and role in steroidogenesis were further studied. Secreted ILs and steroids were measured by ELISA in cell culture supernatant. IL-8 mRNA was quantified by real-time RT-PCR. H295R cells and human adrenal gland expressed IL-8 mRNA. Angiotensin II, potassium, endothelin-1, IL-1α, IL-1β, TNFα, and Escherichia coli lipopolysaccharide dose-dependently increase IL-8 secretion by H295R cells after 24 h incubation. IL-6 had no effect on IL-8 secretion. Angiotensin II time-dependently increased IL-8 secretion by H295R cells up to 48 h. Angiotensin II caused a biphasic increase in IL-8 mRNA expression with a peak 6 h after stimulation. TNFα synergized angiotensin II, potassium, and IL-1α-mediated IL-8 secretion. IL-8 did not modify aldosterone or cortisol secretion by H295R cells under basal or stimulated (angiotensin II or potassium) conditions. In conclusion, it is demonstrated for the first time that human adrenal cells expressed and secreted IL-8 under the regulation of angiotensin II, potassium, endothelin-1, and immune peptides. Adrenal-secreted IL-8 is one point of convergence between the adrenal gland and the immune system and may have relevance in physiological and pathophysiological conditions associated with increased levels of aldosterone secretagogues and the immune system.

scholarly journals Histamine inhibits adrenocortical cell proliferation but does not affect steroidogenesis

2014 ◽  
Vol 221 (1) ◽  
pp. 15-28 ◽  
Author(s):  
Romina Maria Pagotto ◽  
Elba Nora Pereyra ◽  
Casandra Monzón ◽  
Carolina Mondillo ◽  
Omar Pedro Pignataro
Keyword(s):  
Histidine Decarboxylase ◽  
Inositol Phosphates ◽  
Second Messengers ◽  
Experimental Models ◽  
Adrenocortical Cell ◽  
Adrenocortical Cells ◽  
Tumor Pathology ◽  
Cycle Arrest ◽  
M Phase ◽  
H295r Cells

Histamine (HA) is a neurotransmitter synthesized in most mammalian tissues exclusively by histidine decarboxylase enzyme. Among the plethora of actions mediated by HA, the modulatory effects on steroidogenesis and proliferation in Leydig cells (LCs) have been described recently. To determine whether the effects on LCs reported could be extrapolated to all steroidogenic systems, in this study, we assessed the effect of this amine on adrenal proliferation and steroidogenesis, using two adrenocortical cell lines as experimental models, murine Y1 cells and human NCI-H295R cells. Even when steroidogenesis was not modified by HA in adrenocortical cells, the biogenic amine inhibited the proliferation of H295R cells. This action was mediated by the activation of HRH1 subtype and an increase in the production of inositol phosphates as second messengers, causing cell-cycle arrest in the G2/M phase. These results indicate a new role for HA in the proliferation of human adrenocortical cells that could contribute to a better understanding of tumor pathology as well as to the development of new therapeutic agents.

scholarly journals Comparative Gene Expression Analysis Reveals Mechanism of Pinus contorta Response to the Fungal Pathogen Dothistroma septosporum

2020 ◽  
Author(s):  
Mengmeng Lu ◽  
Nicolas Feau ◽  
Dragana Obreht Vidakovic ◽  
Nicholas Ukrainetz ◽  
Barbara Wong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fungal Pathogen ◽  
Pinus Contorta ◽  
Lodgepole Pine ◽  
Selective Constraint ◽  
Transcriptomic Response ◽  
Gene Expression Response ◽  
Gene Modules ◽  
Expression Response ◽  
Dothistroma Septosporum

Many conifers have distributions that span wide ranges in both biotic and abiotic conditions, but the basis of response to biotic stress has received much less attention than response to abiotic stress. In this study, we investigated the gene expression response of lodgepole pine (Pinus contorta) to attack by the fungal pathogen Dothistroma septosporum, which causes Dothistroma needle blight (DNB), a disease that has caused severe climate-related outbreaks in northwestern British Columbia. We inoculated tolerant and susceptible pines with two D. septosporum isolates and analyzed the differentially expressed genes, differential exon usage, and co-expressed gene modules using RNA-seq data. We found a rapid and strong transcriptomic response in tolerant lodgepole pine samples inoculated with one D. septosporum isolate, and a late and weak response in susceptible samples inoculated with another isolate. We mapped 43 of the DEG- or gene-module-identified genes to the reference plant-pathogen interaction pathway deposited in KEGG database. These genes are present in PAMP-triggered and effector-triggered immunity pathways. Genes comprising pathways and gene modules had signatures of strong selective constraint, while the highly expressed genes in tolerant samples appear to have been favored by selection to counterattack the pathogen. We identified candidate resistance genes that may respond to D. septosporum effectors. Taken together, our results show that gene expression response to D. septosporum infection in lodgepole pine varies both among tree genotypes and pathogen strains, and involves both known candidate genes and a number of genes with previously unknown functions.

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