Dataset Information

Resolvin D1 Alleviates the Lung Ischemia Reperfusion Injury via Complement, Immunoglobulin, TLR4, and Inflammatory Factors in Rats.

ABSTRACT: Lung ischemia-reperfusion injury (LIRI) is still an unsolved medical issue, which negatively affects the prognosis of many lung diseases. The aim of this study is to determine the effects of RvD1 on LIRI and the potential mechanisms involved. The results revealed that the levels of complement, immunoglobulin, cytokines, sICAM-1, MPO, MDA, CINC-1, MCP-1, ANXA-1, TLR4, NF-?Bp65, apoptosis index, and pulmonary permeability index were increased, whereas the levels of SOD, GSH-PX activity, and oxygenation index were decreased in rats with LIRI. Except for ANXA-1, these responses induced by LIRI were significantly inhibited by RvD1 treatment. In addition, LIRI-induced structure damages of lung tissues were also alleviated by RvD1 as shown by H&E staining and transmission electron microscopy. The results suggest that RvD1 may play an important role in protection of LIRI via inhibition of complement, immunoglobulin, and neutrophil activation; down-regulation of TLR4/NF-?B; and the expression of a variety of inflammatory factors.

SUBMITTER: Zhao Q

PROVIDER: S-EPMC4951504 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Resolvin D1 Alleviates the Lung Ischemia Reperfusion Injury via Complement, Immunoglobulin, TLR4, and Inflammatory Factors in Rats.

Zhao Qifeng Q Wu Ji J Lin Zhiyong Z Hua Qingwang Q Zhang Weixi W Ye Leping L Wu Guowei G Du Jie J Xia Jie J Chu Maoping M Hu Xingti X

Inflammation 20160801 4

Lung ischemia-reperfusion injury (LIRI) is still an unsolved medical issue, which negatively affects the prognosis of many lung diseases. The aim of this study is to determine the effects of RvD1 on LIRI and the potential mechanisms involved. The results revealed that the levels of complement, immunoglobulin, cytokines, sICAM-1, MPO, MDA, CINC-1, MCP-1, ANXA-1, TLR4, NF-κBp65, apoptosis index, and pulmonary permeability index were increased, whereas the levels of SOD, GSH-PX activity, and oxygen ...[more]

PMID: 27145782

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Project description:BACKGROUND: Inflammatory reaction in blood-spinal cord barrier (BSCB) plays a crucial role in ischemia/reperfusion (I/R) injury. It has been shown that microglia could be activated through Toll-like receptors (TLRs). Therefore, we hypothesize that TLR4 is involved in the microglial activation and BSCB disruption after I/R. RESULTS: To verify our hypothesis, we analyzed the behavioral data, changes of BSCB permeability, as well as expressions of microglial marker Iba-1 and TLR4 in spinal cord I/R model induced by 14 min aortic occlusion. Double immunostaining reveals that after I/R, Iba-1 immunoreactivity increased gradually 12 h after reperfusion and maintained at a such level throughout 36 h. Such increasing pattern of Iba-1 expression is consistent with the increases in Evan's Blue (EB) extravasation, spinal water content and mechanical allodynia demonstrated by lowed withdrawal threshold to Von Frey filaments. Moreover, double immunostaining suggested that TLR4 was highly expressed in microglia. Intrathecal infusion of minocycline and TAK-242 (TLR4 inhibitor) treatment attenuated I/R-induced allodynia and BSCB leakage. In contrast, LPS induced TLR4 expression aggregated above-mentioned injuries. Furthermore, the nuclear factor-kappa B (NF-?B) activity has a similar profile as TLR4 activity. It is consisted with the results of NF-?B mRNA and protein expression changes and activation of downstream cytokine, IL-1?. Expectedly, intrathecal infusion of pyrrolidine dithiocarbamate (PDTC), a NF-?B inhibitor, showed similar protective effects as minocycline and TAK-242. In addition, our data show that TLR4 closely involved in I/R-induced inflammatory damage induced neuronal apoptosis. Significantly, neutralizing TLR4 function largely reduced neuronal apoptosis determined by NeuN immunoreactivity in ventral gray matter and increased percentage of double-label cells with cleaved caspase3, whereas LPS reversed these effects. Similarly, inhibitions of microglia and NF-?B with minocycline or PDTC treatment accordingly perform the same protective effects on I/R injury. CONCLUSION: The results indicate that compromised BSCB caused by I/R injury lead to spinal microglial activation and TLR4, its membrane-bound receptor, up-regulation, which then initiate neuro-inflammation and neuro-apoptosis via NF-?B/ IL-1? pathway. To inhibit the positive feedback loop of TLR4-microglia-NF-?B/ IL-1? pathway by minocycline, TAK-242 (TLR4 inhibitor) and pyrrolidine dithiocarbamate (PDTC, NF-?B inhibitor) may provide new targets for treating I/R injury in clinic.

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Dataset Information

Resolvin D1 Alleviates the Lung Ischemia Reperfusion Injury via Complement, Immunoglobulin, TLR4, and Inflammatory Factors in Rats.

Publications

Resolvin D1 Alleviates the Lung Ischemia Reperfusion Injury via Complement, Immunoglobulin, TLR4, and Inflammatory Factors in Rats.

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