Identification of whole blood mRNA and microRNA biomarkers of tissue damage and immune function resulting from amphetamine exposure or heat stroke in adult male rats

Abstract

This work extends the understanding of how toxic exposures to amphetamine (AMPH) adversely affect the immune system and lead to tissue damage. Importantly, it determines which effects of AMPH are and are not due to pronounced hyperthermia. Whole blood messenger RNA (mRNA) and whole blood and serum microRNA (miRNA) transcripts were identified in adult male Sprague-Dawley rats after exposure to toxic AMPH under normothermic conditions, AMPH when it produces pronounced hyperthermia, or environmentally-induced hyperthermia (EIH). mRNA transcripts with large increases in fold-change in treated relative to control rats and very low expression in the control group were a rich source of organ-specific transcripts in blood. When severe hyperthermia was produced by either EIH or AMPH, significant increases in circulating organ-specific transcripts for liver ( Alb , Fbg , F2 ), pancreas ( Spink1 ), bronchi/lungs ( F3 , Cyp4b1 ), bone marrow ( Np4 , RatNP-3b ), and kidney ( Cesl1 , Slc22a8 ) were observed. Liver damage was suggested also by increased miR-122 levels in the serum. Increases in muscle/heart-enriched transcripts were produced by AMPH even in the absence of hyperthermia. Expression increases in immune-related transcripts, particularly Cd14 and Vcan , indicate that AMPH can activate the innate immune system in the absence of hyperthermia. Most transcripts specific for T-cells decreased 50–70% after AMPH exposure or EIH, with the noted exception of Ccr5 and Chst12 . This is probably due to T-cells leaving the circulation and down-regulation of these genes. Transcript changes specific for B-cells or B-lymphoblasts in the AMPH and EIH groups ranged widely from decreasing ≈ 40% ( Cd19 , Cd180 ) to increasing 30 to 100% ( Tk1 , Ahsa1 ) to increasing ≥500% ( Stip1 , Ackr3 ). The marked increases in Ccr2 , Ccr5 , Pld1 , and Ackr3 produced by either AMPH or EIH observed in vivo provide further insight into the initial immune system alterations that result from methamphetamine and AMPH abuse and could modify risk for HIV and other viral infections.

Hepatic miR-122 expression correlated with IL-28B genetic polymorphisms in hepatocellular carcinoma patients with living donor liver transplantation

“…According to our results, miR-122 expression showed large increases in the liver tissue and very low increases in the plasma in LDLT patients, which agrees with a previous study in adult male rats [9]. Particularly hepatic miR-122 was detected in the native liver following LDLT.…”

Exosomes Derived From Heat Stroke Cases Carry miRNAs Associated With Inflammation and Coagulation Cascade

“…Gene expression profiles in the lung tissue of an HS rat model showed that the miRNAs associated with inflammatory/immune responses, including leukocyte migration, lipopolysaccharide response, NIK/NF-kappaB signaling, and response to reactive oxygen species, were upregulated, which is in agreement with our findings (18). Whole blood mRNA and microRNA have been identified as biomarkers of tissue damage and immune function resulting from HS (19).…”

Exosomes Derived From Heat Stroke Cases Carry miRNAs Associated With Inflammation and Coagulation Cascade

“…The gene expression pro les in lung of a HS rat model reveals that the miRNAs related to in ammatory/immune responses, including leukocyte migration, response to lipopolysaccharide, NIK/NF-kappaB signaling, and response to reactive oxygen species, are up-regulated, which is consistent with our results [11]. Whole blood mRNA and microRNA was identi ed as biomarkers of tissue damage and immune function resulting from heat stroke exposure [12].…”