Exopolysaccharide from Paecilomyces lilacinus modulates macrophage activities through the TLR4/NF‑κB/MAPK pathway

He,Chao; Lin,Hai‑Yan; Wang,Cai‑Chun; Zhang,Ming; Lin,Ying‑Ying; Huang,Feng‑Ying; Lin,Ying‑Zi; Tan,Guang‑Hong

doi:10.3892/mmr.2019.10746

Exopolysaccharide from Paecilomyces lilacinus modulates macrophage activities through the TLR4/NF‑κB/MAPK pathway

Authors:
- Chao He
- Hai‑Yan Lin
- Cai‑Chun Wang
- Ming Zhang
- Ying‑Ying Lin
- Feng‑Ying Huang
- Ying‑Zi Lin
- Guang‑Hong Tan
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Affiliations: Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou, Hainan 571199, P.R. China
Published online on: October 15, 2019 https://doi.org/10.3892/mmr.2019.10746
Pages: 4943-4952
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple exopolysaccharides (EPSs) have been isolated from various organisms in extreme environments and have yielded a variety of activities. The present study evaluated the immunomodulatory capabilities of an EPS (termed PH‑EPS) derived from the fungus Paecilomyces lilacinus PH0016, which was isolated from a tropical and hyperhaline environment in southern China. The macrophage RAW 264.7 cell line was used to investigate the mechanism of PH‑EPS‑induced macrophage activation. The results indicated that RAW 264.7 macrophages were activated by PH‑EPS, in an effect slightly inferior to lipopolysaccharide (LPS), as evidenced by secretion of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α and nitric oxide (NO), and by significantly increased phagocytosis in the cells treated with PH‑EPS. Nuclear factor (NF)‑κB p65 was significantly translocated into the nucleus in the PH‑EPS‑treated cells. In addition, expression of inducible NO synthase (iNOS) and IκB‑α degradation were enhanced in PH‑EPS‑treated cells. The phosphorylation levels of p38, JNK and ERK were also significantly increased in the PH‑EPS‑treated cells. Furthermore, IL‑1β and TNF‑α production was markedly decreased in PH‑EPS‑treated cells when the mitogen‑activated protein kinase (MAPK) pathways were blocked by the inhibitor Dectin‑1 and by antibodies against Toll‑like receptor 4 (TLR4). The present results indicated that PH‑EPS from Paecilomyces lilacinus possessed the capability of activating RAW 264.7 cells via the TLR4/NF‑κB/MAPKs signaling pathway.

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1	Gordon S and Plüddemann A: Tissue macrophages: Heterogeneity and functions. BMC Biol. 15:532017. View Article : Google Scholar : PubMed/NCBI
2	Varin A and Gordon S: Alternative activation of macrophages: Immune function and cellular biology. Immunobiology. 214:630–641. 2009. View Article : Google Scholar : PubMed/NCBI
3	Navegantes KC, de Souza Gomes R, Pereira PAT, Czaikoski PG, Azevedo CHM and Monteiro MC: Immune modulation of some autoimmune diseases: The critical role of macrophages and neutrophils in the innate and adaptive immunity. J Transl Med. 15:362017. View Article : Google Scholar : PubMed/NCBI
4	Mosser DM and Edwards JP: Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 8:958–969. 2008. View Article : Google Scholar : PubMed/NCBI
5	Kim HS, Kim YJ, Lee HK, Ryu HS, Kim JS, Yoon MJ, Kang JS, Hong JT, Kim Y and Han SB: Activation of macrophages by polysaccharide isolated from Paecilomyces cicadae through toll-like receptor 4. Food Chem Toxicol. 50:3190–3197. 2012. View Article : Google Scholar : PubMed/NCBI
6	Li J, Qian W, Xu Y, Chen G, Wang G, Nie S, Shen B, Zhao Z, Liu C and Chen K: Activation of RAW 264.7 cells by a polysaccharide isolated from Antarctic bacterium Pseudoaltermonas sp. S-5. Carbohydr Polym. 130:97–103. 2015. View Article : Google Scholar : PubMed/NCBI
7	Laplante P, Amireault P, Subang R, Dieudé M, Levine JS and Rauch J: Interaction of β2-glycoprotein I with lipopolysaccharide leads to Toll-like receptor 4 (TLR4)-dependent activation of macrophages. J Biol Chem. 286:42494–42503. 2011. View Article : Google Scholar : PubMed/NCBI
8	Chen LF and Greene WC: Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation. J Mol Med (Berl). 81:549–557. 2003. View Article : Google Scholar : PubMed/NCBI
9	Hayden MS and Ghosh S: Signaling to NF-kappaB. Genes Dev. 18:2195–2224. 2004. View Article : Google Scholar : PubMed/NCBI
10	Baldwin AS Jr: The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu Rev Immunol. 14:649–683. 1996. View Article : Google Scholar : PubMed/NCBI
11	Lee JS, Kwon DS, Lee KR, Park JM, Ha SJ and Hong EK: Mechanism of macrophage activation induced by polysaccharide from Cordyceps militaris culture broth. Carbohydr Polym. 120:29–37. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ayoub SS, Botting RM, Joshi AN, Seed MP and Colville-Nash PR: Activation of macrophage peroxisome proliferator-activated receptor-gamma by diclofenac results in the induction of cyclooxygenase-2 protein and the synthesis of anti-inflammatory cytokines. Mol Cell Biochem. 327:101–110. 2009. View Article : Google Scholar : PubMed/NCBI
13	Skeen MJ, Miller MA, Shinnick TM and Ziegler HK: Regulation of murine macrophage IL-12 production. Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines. J Immunol. 156:1196–1206. 1996.PubMed/NCBI
14	Takeuchi O and Akira S: Toll-like receptors; their physiological role and signal transduction system. Int Immunopharmacol. 1:625–635. 2001. View Article : Google Scholar : PubMed/NCBI
15	Wang G, Zhu L, Yu B and Chen K, Liu B, Liu J, Qin G, Liu C, Liu H and Chen K: Exopolysaccharide from Trichoderma pseudokoningii induces macrophage activation. Carbohydr Polym. 149:112–120. 2016. View Article : Google Scholar : PubMed/NCBI
16	Paynich ML, Jones-Burrage SE and Knight KL: Exopolysaccharide from bacillus subtilis induces anti-inflammatory M2 macrophages that prevent T cell-mediated disease. J Immunol. 198:2689–2698. 2017. View Article : Google Scholar : PubMed/NCBI
17	Zhu Y, Wang C, Jia S, Wang B, Zhou K, Chen S, Yang Y and Liu S: Purification, characterization and antioxidant activity of the exopolysaccharide from Weissella cibaria SJ14 isolated from Sichuan paocai. Int J Biol Macromol. 115:820–828. 2018. View Article : Google Scholar : PubMed/NCBI
18	Yamac M, Kanbak G, Zeytinoglu M, Bayramoglu G, Senturk H and Uyanoglu M: Hypoglycemic effect of Lentinus strigosus (Schwein.) Fr. crude exopolysaccharide in streptozotocin-induced diabetic rats. J Med Food. 11:513–517. 2008. View Article : Google Scholar : PubMed/NCBI
19	Wang YX, Hu HY, Yang W, et al: The in vitro anti-HSV-1 action of an EPS extract made from Paecilomyces lilacinus isolated from mangr soil. J Pathog Biol (China). 12:5–9. 2014.(In Chinese).
20	Li GJ, Chang C, Ge TT, et al: Anti-HSV-1 activity in vitro of extracellular polysaccharides from Paecilomyces Lilacinuson isolated from mangrove. Shanxi Med J (China). 46:123–126. 2017.(In Chinese).
21	Hu HY, Wang HM, Lin YZ, Chang CH, Yang W and Wang YX: Effects of extracellular polysaccharides from Paecilomyces Lilacinuson on function of mouse bone marrow-derived dendritic cells. Chin J Immunol. 33:212–216. 2017.(In Chinese).
22	Peixoto E, Oliveira JC, Antas PR and Borba CM: In-vitro study of the host-parasite interactions between mouse macrophages and the opportunistic fungus Paecilomyces lilacinus. Ann Trop Med Parasitol. 104:529–534. 2010. View Article : Google Scholar : PubMed/NCBI
23	Huang FY, Huang FR, Chen B, Liu Q, Wang H, Zhou SL, Zhao HG, Huang YH, Lin YY and Tan GH: Microencapsulation of tumor lysates and live cell engineering with MIP-3α as an effective vaccine. Biomaterials. 53:554–565. 2015. View Article : Google Scholar : PubMed/NCBI
24	Liang TW and Wang SL: Recent advances in exopolysaccharides from Paenibacillus spp.: Production, isolation, structure, and bioactivities. Mar Drugs. 13:1847–1863. 2015. View Article : Google Scholar : PubMed/NCBI
25	Liu J, Wang X, Pu H, Liu S, Kan J and Jin C: Recent advances in endophytic exopolysaccharides: Production, structural characterization, physiological role and biological activity. Carbohydr Polym. 157:1113–1124. 2017. View Article : Google Scholar : PubMed/NCBI
26	Moscovici M: Present and future medical applications of microbial exopolysaccharides. Front Microbiol. 6:10122015. View Article : Google Scholar : PubMed/NCBI
27	Li P and Wang F: Polysaccharides: Candidates of promising vaccine adjuvants. Drug Discov Ther. 9:88–93. 2015. View Article : Google Scholar : PubMed/NCBI
28	Glucksam-Galnoy Y, Sananes R, Silberstein N, Krief P, Kravchenko VV, Meijler MM and Zor T: The bacterial quorum-sensing signal molecule N-3-oxo- dodecanoyl-L-homoserine lactone reciprocally modulates pro- and anti-inflammatory cytokines in activated macrophages. J Immunol. 191:337–344. 2013. View Article : Google Scholar : PubMed/NCBI
29	Kleinert H, Schwarz PM and Forstermann U: Regulation of the expression of inducible nitric oxide synthase. Biol Chem. 384:1343–1364. 2003. View Article : Google Scholar : PubMed/NCBI
30	Nworu CS, Ihim SA, Okoye FB, Esimone CO, Adikwu MU and Akah PA: Immunomodulatory and immunorestorative activities of β-D-glucan-rich extract and polysaccharide fraction of mushroom, Pleurutus tuberregium. Pharm Biol. 53:1555–1566. 2015. View Article : Google Scholar : PubMed/NCBI
31	Gupta P and Barthwal MK: IL-1 β genesis: The art of regulating the regulator. Cell Mol Immunol. 15:998–1000. 2018. View Article : Google Scholar : PubMed/NCBI
32	Dinarello CA: Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 27:519–550. 2009. View Article : Google Scholar : PubMed/NCBI
33	Yan Q, Chen X, Gong H, Qiu P, Xiao X, Dang S, Hong A and Ma Y: Delivery of a TNF-α-derived peptide by nanoparticles enhances its antitumor activity by inducing cell-cycle arrest and caspase-dependent apoptosis. FASEB J. 30:fj201800377R2018.(Epub ahead of print).
34	Bergers G and Benjamin LE: Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 3:401–410. 2003. View Article : Google Scholar : PubMed/NCBI
35	Henneke P and Golenbock DT: Phagocytosis, innate immunity, and host-pathogen specificity. J Exp Med. 199:1–4. 2004. View Article : Google Scholar : PubMed/NCBI
36	Hatada EN, Krappmann D and Scheidereit C: NF-kappaB and the innate immune response. Curr Opin Immunol. 12:52–58. 2000. View Article : Google Scholar : PubMed/NCBI
37	Ruimi N, Rwashdeh H, Wasser S, Konkimalla B, Efferth T, Borgatti M, Gambari R and Mahajna J: Daedalea gibbosa substances inhibit LPS-induced expression of iNOS by suppression of NF-kappaB and MAPK activities in RAW 264.7 macrophage cells. Int J Mol Med. 25:421–432. 2010.PubMed/NCBI
38	Johnson GL and Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:1911–1912. 2002. View Article : Google Scholar : PubMed/NCBI
39	Jones E, Adcock IM, Ahmed BY and Punchard NA: Modulation of LPS stimulated NF-kappaB mediated Nitric Oxide production by PKCepsilon and JAK2 in RAW macrophages. J Inflamm (Lond). 4:232007. View Article : Google Scholar : PubMed/NCBI
40	Yoon YD, Kang JS, Han SB, Park SK, Lee HS, Kang JS and Kim HM: Activation of mitogen-activated protein kinases and AP-1 by polysaccharide isolated from the radix of Platycodon grandiflorum in RAW 264.7 cells. Int Immunopharmacol. 4:1477–1487. 2004. View Article : Google Scholar : PubMed/NCBI
41	Park JM, Kunieda T and Kubo T: The activity of Mblk-1, a mushroom body-selective transcription factor from the honeybee, is modulated by the ras/MAPK pathway. J Biol Chem. 278:18689–18694. 2003. View Article : Google Scholar : PubMed/NCBI
42	Agustinho DP, de Oliveira MA, Tavares AH, Derengowski L, Stolz V, Guilhelmelli F, Mortari MR, Kuchler K and Silva-Pereira I: Dectin-1 is required for miR155 upregulation in murine macrophages in response to Candida albicans. Virulence. 8:41–52. 2017. View Article : Google Scholar : PubMed/NCBI
43	Cohen N, Stolarsky-Bennun M, Amir-Kroll H, Margalit R, Nussbaum G, Cohen-Sfady M, Pevsner-Fischer M, Fridkin M, Bercovier H, Eisenbach L, et al: Pneumococcal capsular polysaccharide is immunogenic when present on the surface of macrophages and dendritic cells: TLR4 signaling induced by a conjugate vaccine or by lipopolysaccharide is conducive. J Immunol. 180:2409–2418. 2008. View Article : Google Scholar : PubMed/NCBI
44	Herre J, Gordon S and Brown GD: Dectin-1 and its role in the recognition of beta-glucans by macrophages. Mol Immunol. 40:869–876. 2004. View Article : Google Scholar : PubMed/NCBI
45	Le Cabec V, Carreno S, Moisand A, Bordier C and Maridonneau-Parini I: Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J Immunol. 169:2003–2009. 2002. View Article : Google Scholar : PubMed/NCBI