MicroRNA-155 deficiency attenuates ischemia-reperfusion injury after liver transplantation in mice

Abstract

SummaryLiver ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality after resection surgery, liver transplantation, and hemorrhagic and septic shock. Mir-155 is upregulated by a broad range of inflammatory mediators, and it has been demonstrated to be involved in both innate and adaptive immune responses. However, the role of mir-155 in liver IRI has never been investigated. In this study, mir-155 deficiency protected mice from liver IRI, as shown by lower serum alanine aminotransferase (ALT) levels and Suzuki scores. Mir-155 deficiency results in the development of M2 macrophages, which respond to IR-induced innate immune stimulation by producing a regulatory inflammatory response with higher level of IL-10, but lower levels of TNF-a, IL-6, and IL12p40. Mir-155 deficiency suppresses IL-17 expression, which contributes to the liver IRI development. In our further in vitro study, the results show that the Th17 differentiation is inhibited by SOCS1 overexpression and the promoted M2 macrophage development induced by mir-155 deficiency is abolished by SOCS1 knockdown. In conclusion, mir-155 deficiency attenuates liver IRI through upregulation of SOCS1, and this was associated with promoted M2 macrophage and inhibited Th17 differentiation.

miR-155 Knockdown Protects against Cerebral Ischemia and Reperfusion Injury by Targeting MafB

“…Significant changes have been found in the levels of miR-155 in the hippocampus and blood after cerebral ischemia injury [24]. In hepatic ischemia-reperfusion, the lack of miR-155 can upregulate SOCS-1 expression and reduce the hepatic damage [11]. Maf is a family described as transcriptional activators and MafB plays a crucial part in mediating the inflammatory reaction in immune cells [19].…”

“…Nazari-Jahantigh et al [32] have also confirmed that miR-155 can attenuate the signaling of proinflammatory factor NF-κB by directly inhibiting the expression of BCL-6. Tang et al [11] have identified that miR-155 deficient can upregulate the expression of IL-10 and downregulate the expression of TNFα, IL-6, and IL-12p40 by decreasing ALT levels, so as to regulate the inflammatory reaction and stimulate innate immune to ameliorate liver ischemia. Consistently, our study demonstrated that systematic subjection to miR-155 inhibitor noticeably reduced ischemia-triggered proinflammatory cytokines IL-1β, IL-6, and TNF-α levels and inflammatory enzymes iNOS and COX-2 levels in CIR injury models in vitro and in vivo, while MafB inhibition or miR-155 overexpression can obviously reverse the impact of anti-miR-155 on inhibiting inflammation and then further augment CIR injury.…”

“…MicroRNAs are of length of about 22-25 nucleotides, highly conserved endogenous single-stranded, noncoding small RNAs, which usually bind to the 3′-untranslated region of target mRNAs to inform silenced complex, resulting in transcriptional suppression and degradation of the target RNA and are closely related with the occurrence and development of many diseases [8,9]. Some studies have also demonstrated that miRNAs also participate in the adjustment of brain damage, myocardial ischemia [10], liver ischemia [11], renal ischemia [12], and other aspects of diseases. Jeyaseelan et al [13] have used gene chip technology to detect miRNA expression in cerebral ischemia injury rats and have found that more than 30 kinds of miRNAs expressions change significantly and that these miRNAs may participate in the neuropathy and dysfunction process following CIR.…”

Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy

“…In this case, IL‐2 signal is enhanced by SOCS1 downregulation. miR‐155 deficiency also attenuates liver ischemia‐reperfusion injury through upregulation of SOCS1, which was associated with promotion of M2 macrophage polarization and suppression of Th17 differentiation …”

“…miR-155 deficiency also attenuates liver ischemia-reperfusion injury through upregulation of SOCS1, which was associated with promotion of M2 macrophage polarization and suppression of Th17 differentiation. (41) SOCS1 and Anti-Tumor Immunity SOCS1 is now considered to be an immune checkpoint molecule for anti-tumor immunity, because SOCS1 negatively regulates signaling of IFN-c and IL-12, essential cytokines for anti-tumor immunity. Previously, we and others showed that SOCS1silenced DCs induce stronger anti-tumor immunity.…”