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Licensed Unlicensed Requires Authentication Published by De Gruyter March 21, 2019

Geniposide alleviates lipopolysaccharide (LPS)-induced inflammation by downregulation of miR-27a in rat pancreatic acinar cell AR42J

  • Xiaofen Zhang , Taishan Gao and Yanhua Wang EMAIL logo
From the journal Biological Chemistry

Abstract

Pancreatitis is a disease caused by inflammation of pancreatic acinar cells. Geniposide (GEN) possesses anti-inflammation activities. Hence, we investigated the effects of GEN on lipopolysaccharide (LPS)-stimulated AR42J cells. AR42J cells were stimulated by LPS and then treated with GEN and/or transfected with miR-27a mimic or negative control. Cell viability and cell apoptosis were detected using the Cell Counting Kit-8 and flow cytometry, respectively. All related proteins were measured by Western blot. The expression of miR-27a was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Moreover, the expression of inflammatory cytokines interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP)-1 was analyzed by qRT-PCR and Western blot. LPS significantly decreased cell viability, and enhanced cell apoptosis and IL-6, MCP-1 expression. Then GEN administration alleviated inflammatory injury by increasing cell viability, while reducing apoptosis, and IL-6 and MCP-1 expression. GEN downregulated miR-27a expression which was induced by LPS. Transfection with miR-27a mimic partially eliminated the protective effects of GEN. The phosphorylation of JNK and c-Jun was downregulated by GEN while upregulated by miR-27a overexpression. GEN alleviates LPS-induced AR42J cell injury as evidenced by promoting cell growth, and upregulation of IL-6 and MCP-1. This process might be modulated by down-regulating miR-27a and inactivation of JNK pathway.

  1. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  2. Conflict of interest statement: The authors declare no conflict of interest.

References

Ammann, R.W., Akovbiantz, A., Largiader, F., and Schueler, G. (1984). Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients. Gastroenterology 86, 820–828.Search in Google Scholar

Anchi, P., Khurana, A., Bale, S., and Godugu, C. (2017). The role of plant-derived products in pancreatitis: experimental and clinical evidence. Phytother. Res. 31, 591–623.10.1002/ptr.5792Search in Google Scholar PubMed

Bhatia, M. (2005). Inflammatory response on the pancreatic acinar cell injury. Scand. J. Surg. 94, 97–102.10.1177/145749690509400203Search in Google Scholar PubMed

Bradley, E.L., 3rd. (1993). A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch. Surg. 128, 586–590.10.1001/archsurg.1993.01420170122019Search in Google Scholar PubMed

Cheng, Y., Kuang, W., Hao, Y., Zhang, D., Lei, M., Du, L., Jiao, H., Zhang, X., and Wang, F. (2012). Downregulation of miR-27a* and miR-532-5p and upregulation of miR-146a and miR-155 in LPS-induced RAW264.7 macrophage cells. Inflammation 35, 1308–1313.10.1007/s10753-012-9443-8Search in Google Scholar PubMed

Chou, C.H., Chang, N.W., Shrestha, S., Hsu, S.D., Lin, Y.L., Lee, W.H., Yang, C.D., Hong, H.C., Wei, T.Y., Tu, S.J., et al. (2016). miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 44, D239–D247.10.1093/nar/gkv1258Search in Google Scholar PubMed PubMed Central

Feng, J., Iwama, A., Satake, M., and Kohu, K. (2009). MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1. Br. J. Haematol. 145, 412–423.10.1111/j.1365-2141.2009.07632.xSearch in Google Scholar PubMed

Fu, Y., Liu, B., Liu, J., Liu, Z., Liang, D., Li, F., Li, D., Cao, Y., Zhang, X., Zhang, N., et al. (2012). Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models. Int. Immunopharmacol. 14, 792–798.10.1016/j.intimp.2012.07.006Search in Google Scholar PubMed

Fu, Q., Qin, T., Chen, L., Liu, C.J., Zhang, X., Wang, Y.Z., Hu, M.X., Chu, H.Y., and Zhang, H.W. (2016). miR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene. World J. Gastroenterol. 22, 4881–4890.10.3748/wjg.v22.i20.4881Search in Google Scholar PubMed PubMed Central

Il’in, D.A., Arkhipov, S.A., and Shkurupy, V.A. (2016). In vitro study of cytophysiological characteristics of multinuclear macrophages from intact and BCG-infected mice. Bull. Exp. Biol. Med. 160, 668–671.10.1007/s10517-016-3245-1Search in Google Scholar PubMed

Jia, Y.J., Jiang, M.N., and De-Kai, P. (1996). Effects of Gardenia jasminoides Ellis on the membranous functions of pancreatic cell in acute pancreatitis. Chinese Journal of Surgery of Integrated Traditional & Western Medicine. 2, 176–178.Search in Google Scholar

Kapoor, M., Martel-Pelletier, J., Lajeunesse, D., Pelletier, J.P., and Fahmi, H. (2011). Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol. 7, 33–42.10.1038/nrrheum.2010.196Search in Google Scholar PubMed

Koo, H.J., Lee, S., Shin, K.H., Kim, B.C., Lim, C.J., and Park, E.H. (2004). Geniposide, an anti-angiogenic compound from the fruits of Gardenia jasminoides. Planta Med. 70, 467–469.10.1055/s-2004-818978Search in Google Scholar PubMed

Koo, H.J., Lim, K.H., Jung, H.J., and Park, E.H. (2006). Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J. Ethnopharmacol. 103, 496–500.10.1016/j.jep.2005.08.011Search in Google Scholar PubMed

Li, X.Q., Lv, H.W., Wang, Z.L., Tan, W.F., Fang, B., and Ma, H. (2015). MiR-27a ameliorates inflammatory damage to the blood-spinal cord barrier after spinal cord ischemia: reperfusion injury in rats by downregulating TICAM-2 of the TLR4 signaling pathway. J. Neuroinflamm. 12, 25.10.1186/s12974-015-0246-3Search in Google Scholar PubMed PubMed Central

Liu, J., Yin, F., Zheng, X., Jing, J., and Hu, Y. (2007). Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. Neurochem. Int. 51, 361–369.10.1016/j.neuint.2007.04.021Search in Google Scholar PubMed

Liu, J.H., Yin, F., Guo, L.X., Deng, X.H., and Hu, Y.H. (2009). Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacol. Sin. 30, 159–165.10.1038/aps.2008.25Search in Google Scholar PubMed PubMed Central

Liu, H.T., He, J.L., Li, W.M., Yang, Z., Wang, Y.X., Yin, J., Du, Y.G., and Yu, C. (2010). Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways. Inflamm. Res. 59, 451–461.10.1007/s00011-009-0118-3Search in Google Scholar PubMed

Liu, C., Hao, Y., Yin, F., Zhang, Y., and Liu, J. (2017). Geniposide protects pancreatic β cells from high glucose-mediated injury by activation of AMP-activated protein kinase. Cell Biol. Int. 41, 544–554.10.1002/cbin.10758Search in Google Scholar PubMed

Paludan, S.R. (2000). Synergistic action of pro-inflammatory agents: cellular and molecular aspects. J. Leukoc. Biol. 67, 18–25.10.1002/jlb.67.1.18Search in Google Scholar PubMed

Samuel, I., Zaheer, S., Fisher, R.A., and Zaheer, A. (2003). Cholinergic receptor induction and JNK activation in acute pancreatitis. Am. J. Surg. 186, 569–574.10.1016/j.amjsurg.2003.07.016Search in Google Scholar PubMed

Shah, A.U., Sarwar, A., Orabi, A.I., Gautam, S., Grant, W.M., Park, A.J., Shah, A.U., Liu, J., Mistry, P.K., Jain, D., et al. (2009). Protease activation during in vivo pancreatitis is dependent on calcineurin activation. Am. J. Physiol. Gastrointest. Liver Physiol. 297, G967–G973.10.1152/ajpgi.00181.2009Search in Google Scholar PubMed PubMed Central

Shi, Q., Cao, J., Fang, L., Zhao, H., Liu, Z., Ran, J., Zheng, X., Li, X., Zhou, Y., Ge, D., et al. (2014). Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by downregulating NF-κB, MAPK and AP-1 signaling pathways in macrophages. Int. Immunopharmacol. 20, 298–306.10.1016/j.intimp.2014.04.004Search in Google Scholar PubMed

Shyu, J.Y., Sainani, N.I., Sahni, V.A., Chick, J.F., Chauhan, N.R., Conwell, D.L., Clancy, T.E., Banks, P.A., and Silverman, S.G. (2014). Necrotizing pancreatitis: diagnosis, imaging, and intervention. Radiographics 34, 1218–1239.10.1148/rg.345130012Search in Google Scholar PubMed

Song, X., Zhang, W., Wang, T., Jiang, H., Zhang, Z., Fu, Y., Yang,Z., Cao, Y., and Zhang, N. (2014). Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation 37, 1588–1598.10.1007/s10753-014-9885-2Search in Google Scholar PubMed

Su, C., Yang, X., and Lou, J. (2016). Geniposide reduces α-synuclein by blocking microRNA-21/lysosome-associated membrane protein 2A interaction in Parkinson disease models. Brain Res. 1644, 98–106.10.1016/j.brainres.2016.05.011Search in Google Scholar PubMed

Su, Q., Yao, J., and Sheng, C. (2018). Geniposide attenuates LPS-induced injury via Up-regulation of miR-145 in H9c2 cells. Inflammation 41, 1229–1237.10.1007/s10753-018-0769-8Search in Google Scholar PubMed

Viola, A. and Luster, A.D. (2008). Chemokines and their receptors: drug targets in immunity and inflammation. Annu. Rev. Pharmacol. Toxicol. 48, 171–197.10.1146/annurev.pharmtox.48.121806.154841Search in Google Scholar PubMed

Wagner, A.C., Mazzucchelli, L., Miller, M., Camoratto, A.M., and Goke, B. (2000). CEP-1347 inhibits caerulein-induced rat pancreatic JNK activation and ameliorates caerulein pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 278, G165–G172.10.1152/ajpgi.2000.278.1.G165Search in Google Scholar PubMed

Wang, Z., Ruan, Z., Mao, Y., Dong, W., Zhang, Y., Yin, N., and Jiang,L. (2014). miR-27a is up regulated and promotes inflammatory response in sepsis. Cell Immunol. 290, 190–195.10.1016/j.cellimm.2014.06.006Search in Google Scholar PubMed

Wang, J., Zhang, Y., Liu, R., Li, X., Cui, Y., and Qu, L. (2015). Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes. Can. J. Physiol. Pharmacol. 93, 261–267.10.1139/cjpp-2014-0536Search in Google Scholar PubMed

Wang, Y., Zhang, X., and Li, C. (2017). Applying Hot Compresses with rhubarb and mirabilite to reduce pancreatic leakage occurrence in the treatment of severe acute pancreatitis. Iran J. Public Health 46, 136–138.Search in Google Scholar

Wang, J., Li, D., Hou, J., and Lei, H. (2018). Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA1555p inhibition. Mol. Med. Rep. 17, 3186–3193.Search in Google Scholar

Windisch, O., Heidegger, C.P., Giraud, R., Morel, P., and Buhler, L. (2016). Thoracic epidural analgesia: a new approach for the treatment of acute pancreatitis? Crit. Care. 20, 116.10.1186/s13054-016-1292-7Search in Google Scholar PubMed PubMed Central

Working Group IAP/APA Acute Pancreatitis Guidelines. (2013). IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 13, e1–e15.10.1016/j.pan.2013.07.063Search in Google Scholar PubMed

Xiaofeng, Y., Qinren, C., Jingping, H., Xiao, C., Miaomiao, W., Xiangru, F., Xianxing, X., Meixia, H., Jing, L., Jingyuan, W., et al. (2012). Geniposide, an iridoid glucoside derived from Gardenia jasminoides, protects against lipopolysaccharide-induced acute lung injury in mice. Planta Med. 78, 557–564.10.1055/s-0031-1298212Search in Google Scholar PubMed

Xie, N., Cui, H., Banerjee, S., Tan, Z., Salomao, R., Fu, M., Abraham, E., Thannickal, V.J., and Liu, G. (2014). miR-27a regulates inflammatory response of macrophages by targeting IL-10. J. Immunol. 193, 327–334.10.4049/jimmunol.1400203Search in Google Scholar PubMed PubMed Central

Yang, L., Ling, Y., Zhang, Z., Zhao, Q., Tang, J., Ji, H., and Zhang,Y. (2011). ZL11n is a novel nitric oxide-releasing derivative of farnesylthiosalicylic acid that induces apoptosis in human hepatoma HepG2 cells via MAPK/mitochondrial pathways. Biochem. Biophys. Res. Commun. 409, 752–757.10.1016/j.bbrc.2011.05.083Search in Google Scholar PubMed

Zhang, X.P., Shi, Y., and Zhang, L. (2007). Progress in the study of therapeutic effects of traditional Chinese medicine and extracts in treating severe acute pancreatitis. J. Pancreas 8, 704–714.Search in Google Scholar

Zhang, X., Lu, H., Wang, Y., Liu, C., Zhu, W., Zheng, S., and Wan, F. (2015). Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria. Int. J. Mol. Med. 35, 218–226.10.3892/ijmm.2014.2002Search in Google Scholar PubMed

Zheng, L., Xue, J., Jaffee, E.M., and Habtezion, A. (2013). Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma. Gastroenterology 144, 1230–1240.10.1053/j.gastro.2012.12.042Search in Google Scholar PubMed PubMed Central

Zhu, S., Ashok, M., Li, J., Li, W., Yang, H., Wang, P., Tracey, K.J., Sama, A.E., and Wang, H. (2009). Spermine protects mice against lethal sepsis partly by attenuating surrogate inflammatory markers. Mol. Med. 15, 275–282.10.2119/molmed.2009.00062Search in Google Scholar PubMed PubMed Central

Received: 2018-11-05
Accepted: 2019-03-15
Published Online: 2019-03-21
Published in Print: 2019-07-26

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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