Chlorogenic acid suppresses lipopolysaccharide‑induced nitric oxide and interleukin‑1β expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells

Kim,Sang‑Hun; Park,Sun‑Young; Park,Young‑Lan; Myung,Dae‑Seong; Rew,Jong‑Sun; Joo,Young‑Eun

doi:10.3892/mmr.2017.7686

Chlorogenic acid suppresses lipopolysaccharide‑induced nitric oxide and interleukin‑1β expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells

Authors:
- Sang‑Hun Kim
- Sun‑Young Park
- Young‑Lan Park
- Dae‑Seong Myung
- Jong‑Sun Rew
- Young‑Eun Joo
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Affiliations: Department of Internal Medicine, Chonnam National University Medical School, Dong‑Ku, Gwangju 501‑757, Republic of Korea
Published online on: October 2, 2017 https://doi.org/10.3892/mmr.2017.7686
Pages: 9224-9232

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Abstract

Chlorogenic acid (CA) is a phenolic compound purified from coffee, fruits and their associated beverages, which possess various biological properties, such as antioxidant and anticarcinogenic activities. The present study evaluated the effects of CA on lipopolysaccharide (LPS)‑induced inflammation in RAW264.7 cells and the associated intracellular signaling pathways using reverse transcription‑quantitative polymerase chain reaction, western blotting and enzyme‑linked immunosorbent assays. CA pretreatment inhibited LPS‑induced expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and pro‑inflammatory mediators including interleukin (IL)‑6, tumor necrosis factor‑α (TNF‑α), macrophage inflammatory protein‑2 (MIP‑2) and IL‑1β in RAW264.7 cells. In addition, phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) with LPS was inhibited by CA pretreatment. CA and STAT3 inhibitor (STAT3i) pretreatment inhibited LPS‑induced nuclear translocation of phosphorylated STAT3. In addition, STAT3i inhibited the LPS‑induced expression of iNOS, NO and IL‑1β similar to the results of CA pretreatment. By contrast, STAT3i did not inhibit the LPS‑induced increase in IL‑6, TNF‑α and MIP‑2 expression. These results indicate that CA may suppress LPS‑induced NO and IL‑1β expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells.

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1	Trendowski M: Recent advances in the development of antineoplastic agents derived from natural products. Drugs. 75:1993–2016. 2015. View Article : Google Scholar : PubMed/NCBI
2	Joo YE: Natural product-derived drugs for the treatment of inflammatory bowel diseases. Intest Res. 12:103–109. 2014. View Article : Google Scholar : PubMed/NCBI
3	Kim SB, Park SJ, Chung SH, Hahn KY, Moon DC, Hong SP, Cheon JH, Kim T and Kim WH: Vaccination and complementary and alternative medicine in patients with inflammatory bowel disease. Intest Res. 12:124–130. 2014. View Article : Google Scholar : PubMed/NCBI
4	Kang NJ, Lee KW, Kim BH, Bode AM, Lee HJ, Heo YS, Boardman L, Limburg P, Lee HJ and Dong Z: Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis. 32:921–928. 2011. View Article : Google Scholar : PubMed/NCBI
5	Svilaas A, Sakhi AK, Andersen LF, Svilaas T, Ström EC, Jacobs DR Jr, Ose L and Blomhoff R: Intakes of antioxidants in coffee, wine, and vegetables are correlated with plasma carotenoids in humans. J Nutr. 134:562–567. 2004.PubMed/NCBI
6	Ludwig IA, Clifford MN, Lean ME, Ashihara H and Crozier A: Coffee: Biochemistry and potential impact on health. Food Funct. 5:1695–1717. 2014. View Article : Google Scholar : PubMed/NCBI
7	Bøhn SK, Blomhoff R and Paur I: Coffee and cancer risk, epidemiological evidence, and molecular mechanisms. Mol Nutr Food Res. 58:915–930. 2014. View Article : Google Scholar : PubMed/NCBI
8	Liang N and Kitts DD: Role of chlorogenic acids in controlling oxidative and inflammatory stress conditions. Nutrients. 8:pii: E162015. View Article : Google Scholar
9	Upadhyay R and Rao LJ Mohan: An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities. Crit Rev Food Sci Nutr. 53:968–984. 2013. View Article : Google Scholar : PubMed/NCBI
10	Weng CJ and Yen GC: Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: Phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treat Rev. 38:76–87. 2012. View Article : Google Scholar : PubMed/NCBI
11	Kim YJ, Chang SY and Ko HJ: Myeloid-derived suppressor cells in inflammatory bowel disease. Intest Res. 13:105–111. 2015. View Article : Google Scholar : PubMed/NCBI
12	Strober W, Fuss I and Mannon P: The fundamental basis of inflammatory bowel disease. J Clin Invest. 117:514–521. 2007. View Article : Google Scholar : PubMed/NCBI
13	Podolsky DK and Xavier RJ: Unravelling the pathogenesis of inflammatory bowel disease. Nature. 448:427–434. 2007. View Article : Google Scholar : PubMed/NCBI
14	Lee SH: Intestinal permeability regulation by tight junction: Implication on inflammatory bowel diseases. Intest Res. 13:11–18. 2015. View Article : Google Scholar : PubMed/NCBI
15	Morris MC, Gilliam EA and Li L: Innate immune programing by endotoxin and its pathological consequences. Front Immunol. 5:6802015. View Article : Google Scholar : PubMed/NCBI
16	Han DS: Current status and prospects of intestinal microbiome studies. Intest Res. 12:178–183. 2014. View Article : Google Scholar : PubMed/NCBI
17	Yu Z, Zhang W and Kone BC: Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem J. 367:97–105. 2002. View Article : Google Scholar : PubMed/NCBI
18	Okugawa S, Ota Y, Kitazawa T, Nakayama K, Yanagimoto S, Tsukada K, Kawada M and Kimura S: Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages. Am J Physiol Cell Physiol. 285:C399–C408. 2003. View Article : Google Scholar : PubMed/NCBI
19	Villarino AV, Kanno Y, Ferdinand JR and O'Shea JJ: Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol. 194:21–27. 2015. View Article : Google Scholar : PubMed/NCBI
20	Zundler S and Neurath MF: Integrating immunologic signaling networks: The JAK/STAT pathway in colitis and colitis-associated cancer. Vaccines (Basel). 4:pii: E52016. View Article : Google Scholar
21	Coskun M, Salem M, Pedersen J and Nielsen OH: Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res. 76:1–8. 2013. View Article : Google Scholar : PubMed/NCBI
22	Danese S, Grisham M, Hodge J and Telliez JB: JAK inhibition using tofacitinib for inflammatory bowel disease treatment: A hub for multiple inflammatory cytokines. Am J Physiol Gastrointest Liver Physiol. 310:G155–G162. 2016.PubMed/NCBI
23	Vuitton L, Koch S and Peyrin-Biroulet L: Janus kinase inhibition with tofacitinib: Changing the face of inflammatory bowel disease treatment. Curr Drug Targets. 14:1385–1391. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kim SF: The nitric oxide-mediated regulation of prostaglandin signaling in medicine. Vitam Horm. 96:211–245. 2014. View Article : Google Scholar : PubMed/NCBI
25	Salvemini D, Kim SF and Mollace V: Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: Relevance and clinical implications. Am J Physiol Regul Integr Comp Physiol. 304:R473–R487. 2013. View Article : Google Scholar : PubMed/NCBI
26	Kim SF: The role of nitric oxide in prostaglandin biology; update. Nitric Oxide. 25:255–264. 2011. View Article : Google Scholar : PubMed/NCBI
27	Gądek-Michalska A, Tadeusz J, Rachwalska P and Bugajski J: Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep. 65:1655–1662. 2013. View Article : Google Scholar : PubMed/NCBI
28	Krakauer T: The polyphenol chlorogenic acid inhibits staphylococcal exotoxin-induced inflammatory cytokines and chemokines. Immunopharmacol Immunotoxicol. 24:113–119. 2002. View Article : Google Scholar : PubMed/NCBI
29	Wei J and Feng J: Signaling pathways associated with inflammatory bowel disease. Recent Pat Inflamm Allergy Drug Discov. 4:105–117. 2010. View Article : Google Scholar : PubMed/NCBI
30	Karrasch T and Jobin C: NF-kappaB and the intestine: Friend or foe? Inflamm Bowel Dis. 14:114–124. 2008. View Article : Google Scholar : PubMed/NCBI
31	Broom OJ, Widjaya B, Troelsen J, Olsen J and Nielsen OH: Mitogen activated protein kinases: A role in inflammatory bowel disease? Clin Exp Immunol. 158:272–280. 2009. View Article : Google Scholar : PubMed/NCBI
32	Hwang SJ, Kim YW, Park Y, Lee HJ and Kim KW: Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm Res. 63:81–90. 2014. View Article : Google Scholar : PubMed/NCBI
33	Shan J, Fu J, Zhao Z, Kong X, Huang H, Luo L and Yin Z: Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264.7 cells through suppressing NF-kappaB and JNK/AP-1 activation. Int Immunopharmacol. 9:1042–1048. 2009. View Article : Google Scholar : PubMed/NCBI
34	Ruan Z, Liu S, Zhou Y, Mi S, Liu G, Wu X, Yao K, Assaad H, Deng Z, Hou Y, et al: Chlorogenic acid decreases intestinal permeability and increases expression of intestinal tight junction proteins in weaned rats challenged with LPS. PLoS One. 9:e978152014. View Article : Google Scholar : PubMed/NCBI
35	Shin HS, Satsu H, Bae MJ, Zhao Z, Ogiwara H, Totsuka M and Shimizu M: Anti-inflammatory effect of chlorogenic acid on the IL-8 production in Caco-2 cells and the dextran sulphate sodium-induced colitis symptoms in C57BL/6 mice. Food Chem. 168:167–175. 2015. View Article : Google Scholar : PubMed/NCBI
36	Zatorski H, Sałaga M, Zielińska M, Piechota-Polańczyk A, Owczarek K, Kordek R, Lewandowska U, Chen C and Fichna J: Experimental colitis in mice is attenuated by topical administration of chlorogenic acid. Naunyn Schmiedebergs Arch Pharmacol. 388:643–651. 2015. View Article : Google Scholar : PubMed/NCBI
37	Shen X, Tian Z, Holtzman MJ and Gao B: Cross-talk between interleukin 1beta (IL-1beta) and IL-6 signalling pathways: IL-1beta selectively inhibits IL-6-activated signal transducer and activator of transcription factor 1 (STAT1) by a proteasome-dependent mechanism. Biochem J. 352:913–919. 2000. View Article : Google Scholar : PubMed/NCBI
38	Shi D, Wang Q, Zheng H, Li D, Shen Y, Fu H, Li T, Mei H, Lu G, Qiu Y, et al: Paeoniflorin suppresses IL-6/Stat3 pathway via upregulation of Socs3 in dendritic cells in response to 1-chloro-2,4-dinitrobenze. Int Immunopharmacol. 38:45–53. 2016. View Article : Google Scholar : PubMed/NCBI