Hydrostatin-SN10 Ameliorates Pancreatitis-Induced Lung Injury by Affecting IL-6-Induced JAK2/STAT3-Associated Inflammation and Oxidative Stress

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2019 Dec 13

PMID 31827715

Citations 8

Authors

Xuehua Piao

Yanping Zou

Xiaodan Sui

Baohai Liu

Fanji Meng

Shuangdi Li

Qingyu Zhang

Chi Ma

Tong Wu

Affiliations

Soon will be listed here.

Abstract

Hydrostatin-SN1 (peptide sequence, DEQHLETELHTLTSVLTANGFQ), a kind of peptides extracted from snake venom, has been reported to have anti-inflammatory effect, but its truncated mutant hydrostatin-SN10 (peptide sequence, DEQHLETELH) on pancreatitis-induced acute lung injury has not been well documented. Interleukin- (IL-) 6-induced Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway is involved with inflammatory and oxidative stress activities and may be associated with the pathogenesis of lung injury, and related molecules were measured. Taurocholate-induced pancreatitis associated with acute lung injury was established and treated with hydrostatin-SN10. Pancreatitis was confirmed by measuring the serum levels of amylase, lipase, and trypsinogen and urinary amylase. Lung injury was determined by histologically assessing acinar cell changes. The related molecules of IL-6-induced JAK2/STAT3-associated inflammation and oxidative stress were quantitated by real time-PCR, Western blot, and/or immunochemical assay. Hydrostatin-SN10 reduced the levels of serum amylase, lipase, and trypsinogen and urinary amylase when compared with the model group ( < 0.05). Hydrostatin-SN10 significantly inhibited the IL-6-stimulated JAK2/STAT3 pathway and reduced the number of apoptotic cells via the downregulation of caspase 3 and BAX (proapoptotic) and upregulation of Bcl2 (antiapoptotic) ( < 0.05). IL-6 induced the increase in the levels of JAK2 and STAT3, which was reversed by hydrostatin-SN10 treatment ( < 0.05). In addition, hydrostatin-SN10 reduced the expression of IL-6 and TNF- (tumor necrosis factor-) and increased the level of IL-10 ( < 0.05). On the other hand, hydrostatin-SN10 treatment increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) and the levels of malondialdehyde (MDA) and alanine aminotransferase (ALT) ( < 0.05). These results suggest that hydrostatin-SN10 may inhibit pancreatitis-induced acute lung injury by affecting IL-6-mediated JAK2/STAT3 pathway-associated inflammation and oxidative stress.

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References

Meng X, Hu L, Li W . Baicalin ameliorates lipopolysaccharide-induced acute lung injury in mice by suppressing oxidative stress and inflammation via the activation of the Nrf2-mediated HO-1 signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2019; 392(11):1421-1433. DOI: 10.1007/s00210-019-01680-9. View

Amirshahrokhi K, Khalili A . Carvedilol attenuates paraquat-induced lung injury by inhibition of proinflammatory cytokines, chemokine MCP-1, NF-κB activation and oxidative stress mediators. Cytokine. 2016; 88:144-153. DOI: 10.1016/j.cyto.2016.09.004. View

Springhorn A, Hoppe T . Western blot analysis of the autophagosomal membrane protein LGG-1/LC3 in Caenorhabditis elegans. Methods Enzymol. 2019; 619:319-336. DOI: 10.1016/bs.mie.2018.12.034. View

Han X, Wang Y, Chen H, Zhang J, Xu C, Li J . Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury. Exp Ther Med. 2016; 11(3):788-796. PMC: 4774378. DOI: 10.3892/etm.2016.2988. View

Bhatia M, Proudfoot A, Wells T, Christmas S, Neoptolemos J, Slavin J . Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis. Br J Surg. 2003; 90(6):698-704. DOI: 10.1002/bjs.4102. View

Amiti , Tamizhselvi R, Manickam V . Menadione (vitamin K3) inhibits hydrogen sulfide and substance P via NF-кB pathway in caerulein-induced acute pancreatitis and associated lung injury in mice. Pancreatology. 2019; 19(2):266-273. DOI: 10.1016/j.pan.2019.01.012. View

Li Q, Ye W, Huang Z, Zhang Q, He Y . Effect of IL-6-mediated STAT3 signaling pathway on myocardial apoptosis in mice with dilated cardiomyopathy. Eur Rev Med Pharmacol Sci. 2019; 23(7):3042-3050. DOI: 10.26355/eurrev_201904_17586. View

Shieh J, Tseng H, Jung F, Yang S, Lin J . Elevation of IL-6 and IL-33 Levels in Serum Associated with Lung Fibrosis and Skeletal Muscle Wasting in a Bleomycin-Induced Lung Injury Mouse Model. Mediators Inflamm. 2019; 2019:7947596. PMC: 6458868. DOI: 10.1155/2019/7947596. View

Wu X, Tian F, Su M, Wu M, Huang Y, Hu L . BF211, a derivative of bufalin, enhances the cytocidal effects in multiple myeloma cells by inhibiting the IL-6/JAK2/STAT3 pathway. Int Immunopharmacol. 2018; 64:24-32. DOI: 10.1016/j.intimp.2018.08.016. View

10.

Wei L, Gao J, Zhang S, Wu S, Xie Z, Ling G . Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism. J Biol Chem. 2015; 290(27):16633-52. PMC: 4505416. DOI: 10.1074/jbc.M115.642645. View

11.

Zhou Y, Lv L, Liu Q, Song J . Total flavonoids extracted from function in polycystic ovary syndrome through IL-6 mediated JAK2/STAT3 signaling pathway. Biosci Rep. 2018; 39(1). PMC: 6328881. DOI: 10.1042/BSR20181380. View

12.

Jing W, Qin F, Guo X, Sun Y, Yan C, Qiu C . G-CSF mediates lung injury in mice with adenine-induced acute kidney injury. Int Immunopharmacol. 2018; 63:1-8. DOI: 10.1016/j.intimp.2018.07.032. View

13.

Wu G, Wang J, Luo P, Li A, Tian S, Jiang H . Hydrostatin-SN1, a Sea Snake-Derived Bioactive Peptide, Reduces Inflammation in a Mouse Model of Acute Lung Injury. Front Pharmacol. 2017; 8:246. PMC: 5418923. DOI: 10.3389/fphar.2017.00246. View

14.

Harling K, Adankwah E, Guler A, Afum-Adjei Awuah A, Adu-Amoah L, Mayatepek E . Constitutive STAT3 phosphorylation and IL-6/IL-10 co-expression are associated with impaired T-cell function in tuberculosis patients. Cell Mol Immunol. 2019; 16(3):275-287. PMC: 6460487. DOI: 10.1038/cmi.2018.5. View

15.

Yang M, Wang C, Yang S, Leu C, Chen S, Wu C . IL-6 ameliorates acute lung injury in influenza virus infection. Sci Rep. 2017; 7:43829. PMC: 5338329. DOI: 10.1038/srep43829. View

16.

OGara B, Subramaniam B, Shaefi S, Mueller A, Banner-Goodspeed V, Talmor D . Anesthetics to Prevent Lung Injury in Cardiac Surgery (APLICS): a protocol for a randomized controlled trial. Trials. 2019; 20(1):312. PMC: 6544964. DOI: 10.1186/s13063-019-3400-x. View

17.

Lei S, Su W, Xia Z, Wang Y, Zhou L, Qiao S . Hyperglycemia-Induced Oxidative Stress Abrogates Remifentanil Preconditioning-Mediated Cardioprotection in Diabetic Rats by Impairing Caveolin-3-Modulated PI3K/Akt and JAK2/STAT3 Signaling. Oxid Med Cell Longev. 2019; 2019:9836302. PMC: 6748204. DOI: 10.1155/2019/9836302. View

18.

Tutkun L, Iritas S, Deniz S, Oztan O, Abusoglu S, Unlu A . TNF-α and IL-6 as Biomarkers of Impaired Lung Functions in Dimethylacetamide Exposure. J Med Biochem. 2019; 38(3):276-283. PMC: 6534953. DOI: 10.2478/jomb-2018-0040. View

19.

Gu X, Yu N, Pang X, Zhang W, Zhang J, Zhang Y . EXPRESS: Products of oxidative stress and TRPA1 expression in the brainstem of rats after lung ischemia-reperfusion injury. Pulm Circ. 2019; :2045894019865169. PMC: 6681259. DOI: 10.1177/2045894019865169. View

20.

Liu Z, Gan L, Zhou Z, Jin W, Sun C . SOCS3 promotes inflammation and apoptosis via inhibiting JAK2/STAT3 signaling pathway in 3T3-L1 adipocyte. Immunobiology. 2015; 220(8):947-53. DOI: 10.1016/j.imbio.2015.02.004. View