Early life stress induces immune priming in kidneys of adult male rats

Carmen De Miguel, Ijeoma E. Obi, Dao H. Ho, Analia S. Loria, Jennifer S. Pollock

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Early life stress (ELS) in humans is associated with elevated proinflammatory markers. We hypothesized that ELS induces activation of the immune response in a rat model of ELS, maternal separation (MatSep), in adulthood. MatSep involves separating pups from the dam from postnatal day 2 to postnatal day 14 for 3 h/day. Control rats are nonseparated littermates. We determined circulating and renal immune cell numbers, renal immune cell activation markers, renal cytokine levels, and the renal inflammatory gene expression response to low-dose lipopolysaccharide (LPS) in male MatSep and control rats. We observed that MatSep did not change the percentage of gated events for circulating CD3+, CD4+, CD8+, and CD4+/Foxp3+ cells or absolute numbers of mononuclear and T cells in the circulation and kidneys; however, MatSep led to an increase in activation of renal neutrophils as well as CD44+ cells. Renal toll-like receptor 4 (TLR4) and interleukin 1 beta (IL-1β) was significantly increased in MatSep rats, specifically in the outer and inner medulla and distal nephron, respectively. Evaluation of renal inflammatory genes showed that in response to a low-dose LPS challenge (2 mg/kg iv) a total of 20 genes were significantly altered in kidneys from MatSep rats (17 genes were upregulated and 3 were downregulated), as opposed to no significant differences in gene expression in control vs. control + LPS groups. Taken together, these findings indicate that MatSep induces priming of the immune response in the kidney.

Original languageEnglish
Pages (from-to)F343-F355
JournalAmerican Journal of Physiology - Renal Physiology
Volume314
Issue number3
DOIs
StatePublished - Mar 2018

Bibliographical note

Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.

Keywords

  • Cytokines
  • Early life stress
  • Immune response
  • Kidney
  • Lipopolysaccharide
  • Maternal separation

ASJC Scopus subject areas

  • Physiology
  • Urology

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