Abstract
Toll-like receptors (TLRs) are the key regulators of innate and adaptive immunity and are highly expressed during sepsis. Thus, studying the expression of TLRs in an animal septic model might indicate their possible association with acute kidney injury in sepsis. Seventy-two male C57BL/6J mice were used for this study. Randomly, these animals were divided into 6 groups (N = 12/group): 3 control and 3 septic groups depending on the euthanasia time (24 h, 48 h, 72 h). Septic groups underwent cecal ligation and puncture (CLP) to induce peritonitis, while control groups had a sham operation. Hematological tests were performed in serum for immune biomarkers; immunohistochemistry, morphometry and qRT-PCR analysis were used on both kidney and intestine tissues to evaluate the expression of TLR 2, 3, 4 and 7 in a septic process. At the end of each experimental period, we found that TLRs 2, 3, 4 and 7 were expressed in both tissues but there were differences between those at various time points. Also, we found that mRNA levels were significantly higher in qRT-PCR evaluation in septic groups than control groups in both kidney and intestinal tissues (p < 0.05); showing a steady increase in the septic groups as the time to euthanasia was prolonged (p < 0.05). Overall, our study provides a suggestion that TLRs 2, 3, 4 and 7 are highly expressed in the kidneys of septic mice and especially that these TLRs are sensitive and specific markers for sepsis. Finally, our study supports the diagnostic importance of TLRs in AKI and provides an insight on the contribution of septic mice models in the study of multi organ dysfunction syndrome in general.
Highlights
Toll-like receptors (TLRs) are the key regulators of innate and adaptive immunity and are highly expressed during sepsis
Sepsis is defined as a systemic, dysregulated immunologic host response to infection which can result in multiple organ dysfunction syndrome (MODS) and, often, it is incompatible with life[1,2]
To investigate renal inflammation, neutrophil gelatinase associated-lipocalin (NGAL) and interleukin 18 (IL18) markers were measured and their serum levels were monitored after cecal ligation and puncture (CLP) and sham operation
Summary
Toll-like receptors (TLRs) are the key regulators of innate and adaptive immunity and are highly expressed during sepsis. Studying the expression of TLRs in an animal septic model might indicate their possible association with acute kidney injury in sepsis. Sepsis is defined as a systemic, dysregulated immunologic host response to infection which can result in multiple organ dysfunction syndrome (MODS) and, often, it is incompatible with life[1,2] It remains the primary cause of death in intensive care unit (ICU) patients[3]. It was thought that sepsis-related hemodynamic alterations in the macrocirculation resulting in reduced renal perfusion were responsible for this phenomenon This mechanism has been outdated, and a more complex pathway is suggested; changes in the microcirculation of the kidney along with an exacerbated inflammatory response propose a more accurate, not completely clarified, theory[14]. This strongly suggests the presence of a common pathway between the initial triggers of tubular cell injury and the inflammatory response in the kidney[15,16]
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