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Transcriptome analysis of control and ERK3-depleted Human Colonic Primary Epithelial cells (HCPECs)

ABSTRACT: RNA sequencing analysis of control and ERK3 knockdown HCPECs was performed to understand the physiological relevance of ERK3 in maintaining basal as well as LPS-mediated innate immune responses in HCPECs. Results revealed that ERK3 is required for the regulation of several key cytokines and chemokines even at the steady state. In particular, we discovered that ERK3 is indespansable for the transcriptional regulation of CXCL8/IL-8, CXCL10, MCP-1/CCL2 and GCP-2/CXCL6. Concomitantly, a functional interpretation of the differentially expressed (DE) genes with topGO indicated an important role of ERK3 in regulation of genes involved in, among others, immune responses and leukocyte chemotaxis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136002 | GEO | 2020/04/27

REPOSITORIES: GEO

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Project description:Brucellosis is still a widespread zoonotic disease. Very little is known about the interaction between B. abortus and trophoblastic cells, which is essential for better understanding the pathogenesis of the Brucella-induced placentitis and abortion, a key event for transmission of the disease. The goal of this study was to evaluate the profile of gene expression by bovine trophoblastic cells during infection with B abortus. Explants of chorioallantoic membranes were inoculated with B. abortus strain 2308. Microarray analysis was performed at 4 h after infection, and expression of cytokines and chemokines by trophoblastic cells was assessed by real time RT-PCR at 6 and 12 h after inoculation. In addition, cytokine and chemokine expression was evaluated in placentomes from experimentally infected cows. Expression of pro-inflammatory genes by trophoblastic cells was suppressed at 4 h after inoculation, whereas a significant up-regulation of CXC chemokines, namely CXCL6 (GCP-2) and CXCL8 (IL-8), was observed at 12, but not at 6 h after inoculation. Placentomes of experimentally infected cows had a similar profile of chemokine expression, with upregulation of CXCL6 and CXCL8. Our data indicate that B. abortus modulates the innate immune response by trophoblastic cells, suppressing expression of pro-inflammatory mediators during the early stages of infection that is followed by a delayed and mild expression of pro-inflammatory chemokines, which is similar to the profile of chemokine expression in the placentomes of experimentally infected cows. This trophoblastic response is likely to contribute to the pathogenesis of B. abortus-induced placentitis. Keywords: trophoblast response to Brucella Total RNA used for microarray analysis was obtained from 6 placentas with 12 infected and 12 control explants from each placenta. At 4 h after inoculation, total RNA was isolated from the trophoblastic surface of the explants. Three RNA pools from two placentas each were generated prior to cDNA synthesis.

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Transcriptome analysis of control and ERK3-depleted Human Colonic Primary Epithelial cells (HCPECs)

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