Acute alcohol intoxication impairs sonic hedgehog-GLI1 signaling and activation of primitive hematopoietic precursor cells in the early stage of host response to bacteremia.

Title

Acute alcohol intoxication impairs sonic hedgehog-GLI1 signaling and activation of primitive hematopoietic precursor cells in the early stage of host response to bacteremia.

Creator

Shi X;Simms KJ;Zhang P

Publisher

Alcoholism, Clinical And Experimental Research

Date

2020
2020-08-09

Description

Background: Activation of hematopoietic stem cells [HSCs, lineage(lin) - stem cell growth factor receptor (c-kit) + stem cell antigen-1(Sca-1) + , or LKS cells in mice] is critical for initiating the granulopoietic response. This study determined the effect of alcohol exposure on sonic hedgehog (SHH) signaling in the regulation of HSC activation during bacteremia.; Methods: Acute alcohol intoxication was induced in mice by intraperitoneal (i.p.) injection of 20% alcohol (5 g alcohol/kg body weight). Control mice received i.p. saline. Thirty minutes later, mice were intravenously (i.v.) injected with Escherichia coli (E. coli, 1 to 5 × 10 7 CFUs/mouse) or saline.; Results: SHH expression by lineage-negative bone marrow cells (BMCs) was significantly increased 24 hours after E. coli infection. Extracellular signal-regulated kinase 1/2 (ERK1/2)-specificity protein 1 (Sp1) signaling promotes SHH expression. ERK1/2 was markedly activated in BMCs 8 hours following E. coli infection. Alcohol suppressed both the activation of ERK1/2 and up-regulation of SHH expression following E. coli infection. E. coli infection up-regulated GLI family zinc finger 1 (Gli1) gene expression by BMCs and increased Gli1 protein content in LKS cells. The extent of Gli1 expression was correlated with the activity of proliferation in LKS cells. Alcohol inhibited up-regulation of Gli1 expression and activation of LKS cells in response to E. coli infection. Alcohol also interrupted the granulopoietic response to bacteremia.; Conclusion: These data show that alcohol disrupts SHH-Gli1 signaling and HSC activation in the early stage of the granulopoietic response, which may serve as an important mechanism underlying the impairment of immune defense against bacterial infection in host excessively consuming alcohol. (© 2020 by the Research Society on Alcoholism.)

Subject

Alcohol; Bacteremia; Hematopoietic Stem Cells; Host Response; Sonic Hedgehog

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

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ISSN

1530-0277

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences

Update Year & Number

September 2020 List

Citation

Shi X;Simms KJ;Zhang P, “Acute alcohol intoxication impairs sonic hedgehog-GLI1 signaling and activation of primitive hematopoietic precursor cells in the early stage of host response to bacteremia.,” NEOMED Bibliography Database, accessed June 20, 2021, https://neomed.omeka.net/items/show/11256.

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