Abstract
Lysozyme from hen egg has been reported to possess an anti-inflammatory effect. However, little is known about its detailed mechanism. The mechanism of anti-inflammatory effect of lysozyme was examined in this study. When mouse macrophage-like cell line RAW264.7 cells and mouse peritoneal macrophages were activated with lipopolysaccharide (LPS) and then treated with lysozyme, the production of tumor necrosis factor-α and interleukin-6 was significantly suppressed. The effect was induced by suppressing the gene expression levels of both cytokines. Phagocytosis activity of peritoneal macrophages was not altered by the treatment with lysozyme, suggesting that lysozyme shows the anti-inflammatory effect without inhibiting the phagocytotic response of macrophages. In addition, lysozyme inhibited phosphorylation of c-jun N-terminal kinase (JNK) and was taken up by macrophages within 1 h after treatment of the cells with lysozyme. Overall results suggest that lysozyme is taken up intracellularly and suppresses LPS-induced inflammatory responses by inhibiting JNK phosphorylation.
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References
Carrillo W, García-Ruiz A, Recio I, Moreno-Arribas MV (2014) Antibacterial activity of hen egg white lysozyme modified by heat and enzymatic treatments against oenological lactic acid bacteria and acetic acid bacteria. J Food Prot 77:1732–1739
Carrillo W, Spindola H, Ramos M, Recio I, Carvalho JE (2016) Anti-inflammatory and anti-nociceptive activities of native and modified hen egg white lysozyme. J Med Food 19:978–982
Chung J, Ku SK, Lee S, Bae JS (2016) Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses. Biochem Biophys Res Commun 474:715–721
Coussens LM, Zitvogel L, Palucka AK (2013) Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science 339:286–291
Ding AH, Nathan CF, Stuehr DJ (1988) Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol 141:2407–2412
Han SM, Jung YD, Morel C, Lakhani AS, Kim KJ, Flavell AR, Davis JR (2013) JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339:218–222
Ibrahim HR, Hamasaki K, Miyata T (2017) Novel peptide motifs from lysozyme suppress pro-inflammatory cytokines in macrophages by antagonizing toll-like receptor and LPS-scavenging action. Eur J Pham Sci 107:240–248
Jollès P, Jollès J (1984) What’s new in lysozyme research? Always a model system, today as yesterday. Mol Cell Biochem 63:165–189
Kanda K, Nishi K, Kadota A, Nishimoto S, Liu MC, Sugahara T (2012) Nobiletin suppresses adipocyte differentiation of 3T3-L1 cells by an insulin and IBMX mixture induction. Biochim Biophys Acta 1820:461–468
Kawai T, Takeuchi O, Fujita T, Inoue J, Mühlradt PF, Sato S, Hoshino K, Akira S (2001) Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol 167:5887–5894
Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G (1991) Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 10:4025–4031
Kyriakis MJ, Avruch J (1996) Protein kinase cascades activated by stress and inflammatory cytokines. BioEssays 18:567–577
Lee M, Kovacs-Nolan J, Yang C, Archbold T, Fan MZ, Mine Y (2009) Hen egg lysozyme attenuates inflammation and modulates local gene expression in a porcine model of dextran sodium sulfate (DSS)-induced colitis. J Agric Food Chem 57:2233–2240
Lee W, Ku SK, Na DH, Bae JS (2015) Anti-inflammatory effects of lysozyme against HMGB1 in human endothelial cells and in mice. Inflammation 38:1911–1924
Manabe I (2011) Chronic inflammation links cardiovascular, metabolic and renal diseases. Circ J 75:2739–2748
Murakami F, Sasaki T, Sugahara T (1997) Lysozyme stimulates immunoglobulin production by human-human hybridoma and human peripheral blood lymphocytes. Cytotechnology 24:177–182
Nishi K, Kondo A, Okamoto T, Nakano H, Daifuku M, Nishimoto S, Ochi K, Takaoka T, Sugahara T (2011) Immunostimulatory in vitro and in vivo effects of a water-soluble extract from kale. Biosci Biotechnol Biochem 75:40–46
Ogundele MO (1998) A novel anti-inflammatory activity of lysozyme: modulation of serum complement activation. Mediators Inflamm 7:363–365
Ohbayashi H, Setoguchi Y, Fukuchi Y, Shibata K, Sakata Y, Arai T (2016) Pharmacological effects of lysozyme on COPD and bronchial asthma with sputum: a randomized, placebo-controlled, small cohort, cross-over study. Pulm Pharmacol Ther 37:73–80
Putra ABN, Morishige H, Nishimoto S, Nishi K, Shiraishi R, Doi M, Sugahara T (2012) Effect of collagens from jellyfish and bovine Achilles tendon on the activity of J774.1 and mouse peritoneal macrophage cells. J Funct Foods 4:504–512
Sato S, Sanjo H, Takeda K, Ninomiya-Tsuji J, Yamamoto M, Kawai T, Matsumoto K, Takeuchi O, Akira S (2005) Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat Immunol 6:1087–1095
Schindler H, Lutz MB, Röllinghoff M, Bogdan C (2001) The production of IFN-gamma by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4. J Immunol 166:3075–3082
Sugahara T, Murakami F, Yamada Y, Sasaki T (2000) The mode of actions of lysozyme as an immunoglobulin production stimulating factor. Biochim Biophys Acta 1475:27–34
Sugahara T, Yamada Y, Yano S, Sasaki T (2002) Heat denaturation enhanced immunoglobulin production stimulating activity of lysozyme from hen egg white. Biochim Biophys Acta 1572:19–24
Takada K, Ohno N, Yadomae T (1994) Detoxification of lipopolysaccharide (LPS) by egg white lysozyme. FEMS Immunol Med Microbiol 9:255–263
Vodovotz Y, Bogdan C, Paik J, Xie QW, Nathan C (1993) Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor β. J Exp Med 178:605–613
Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112:1785–1788
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830
Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K, Akira S (2003) TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 4:1144–1150
Yokooji T, Hamura K, Matsuo H (2013) Intestinal absorption of lysozyme, an egg-white allergen, in rats: kinetics and effect of NSAIDs. Biochem Biophys Res Commun 438:61–65
Acknowledgements
This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research C (15K07432). Animal experiments were accomplished at the Division of Genetic Research of the Advanced Research Support Center (ADRES), Ehime University.
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Tagashira, A., Nishi, K., Matsumoto, S. et al. Anti-inflammatory effect of lysozyme from hen egg white on mouse peritoneal macrophages. Cytotechnology 70, 929–938 (2018). https://doi.org/10.1007/s10616-017-0184-2
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DOI: https://doi.org/10.1007/s10616-017-0184-2