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.
|Journal||American Journal of Physiology - Renal Physiology|
|State||Published - Mar 2018|
Bibliographical noteFunding Information:
Portions of this work were funded by National Institute of Diabetes and Digestive and Kidney Diseases Grant T32-DK-007545 to C. De Miguel, the William Townsend Porter Pre-doctoral Fellowship from the American Physiological Society and National Heart, Lung, and Blood Institute Grants T32-HL-007918–19 to I. E. Obi, F32-HL-116145 to D. H. Ho, K99-R00-HL-111354 to A. S. Loria, and P01-HL-69999 to J. S. Pollock.
© 2018 American Physiological Society. All rights reserved.
- Early life stress
- Immune response
- Maternal separation
ASJC Scopus subject areas