Microbiology and Biotechnology Letters (한국미생물·생명공학회지)

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Reconsideration of Classical Antibiotic Lincomycin: Anti-inflammatory Effect in LPS-stimulated RAW 264.7 Cells

  • Yang, Eun-Jin (Department of Chemistry and Cosmetics, Jeju National University) ;
  • Lee, Nari (Department of Chemistry and Cosmetics, Jeju National University) ;
  • Hyun, Chang-Gu (Department of Chemistry and Cosmetics, Jeju National University)
  • Received : 2020.02.20
  • Accepted : 2020.03.26
  • Published : 2020.09.28
Download PDF
⟨ Previous Next ⟩

Abstract

Since, side effects of antibiotics are frequently emphasized these days, their use is gradually diminishing, and alternative drugs are being developed. We have sought to reintroduce them as raw materials for human health as conventional 'weapons' that have been retired after their historical duties. In this study, we investigated the anti-inflammatory effects of lincomycin (LIN), on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our findings show that LIN potently inhibited production of LPS-induced proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), without cytotoxicity. Consistent with these findings, LIN strongly decreased protein expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, LIN reduced pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. To further elucidate the mechanisms of these inhibitory effects of LIN, we studied LPS-induced IκB-α degradation, and mitogen-activated protein kinase (MAPK) phosphorylation. LIN suppressed downregulation of inhibitory κB (IκB-α) degradation, and the phosphorylation of the c-Jun N-terminal kinase (JNK) pathway. Based on these results, we suggest that LIN may be considered a potential candidate as an anti-inflammatory cosmetic or a medicine for human health.

Keywords

References

  1. Udommethaporn S, Tencomnao T, McGowan EM, Boonyaratanakornkit V. 2016. Assessment of anti-TNF-${\alpha}$ activities in keratinocytes expressing inducible TNF- ${\alpha}$: A novel tool for anti-TNF-${\alpha}$ drug screening. PLoS One 11: e0159151. https://doi.org/10.1371/journal.pone.0159151
  2. Lapara NJ 3rd, Kelly BL. 2010. Suppression of LPS-induced inflammatory responses in acrophages infected with Leishmania. J. Inflamm (Lond). 7: 8. https://doi.org/10.1186/1476-9255-7-8
  3. Zhang X, Li N, Shao H, Meng Y, Wang L, Wu Q, et al. 2016. Methane limit LPS-induced NF-${\kappa}B$/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-$3{\beta}$-mediated IL-10 expression. Sci. Rep. 11: 6.
  4. Gao HM, Liu B, Zhang W, Hong JS. 2003. Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol. Sci. 24: 395-401. https://doi.org/10.1016/S0165-6147(03)00176-7
  5. Copeland S, Warren HS, Lowry SF, Calvano SE, Remick D. 2005. Acute inflammatory response to endotoxin in mice and humans. Clin. Diagn. Lab. Immunol. 12: 60-67. https://doi.org/10.1128/CDLI.12.1.60-67.2005
  6. Roos-Engstrand E, Wallin A, Bucht A, Pourazar J, Sandstrom T, Blomberg A. 2005. Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure. Eur. Respir. J. 25: 797-803. https://doi.org/10.1183/09031936.05.00078804
  7. Soromou LW, Zhang Z, Li R, Chen N, Guo W, Huo M, et al. 2012. Regulation of inflammatory cytokines in lipopolysaccharidestimulated RAW 264.7 murine macrophage by 7-O-methylnaringenin. Molecules 17: 3574-3585. https://doi.org/10.3390/molecules17033574
  8. Yang G, Lee K, Lee M, Ham I, Choi HY. 2012. Inhibition of lipopolysaccharide-induced nitric oxide and prostaglandin $E_2$ production by chlo-roform fraction of Cudrania tricuspidata in RAW 264.7 macrophages. BMC Complement. Altern. Med. 12: 250.
  9. Gomez I, Foudi N, Longrois D, Norel X. 2013. The role of prostaglandin $E_2$ in human vascular inflammation. Prostaglandins Leukot. Essent. Fatty Acids 89: 55-63. https://doi.org/10.1016/j.plefa.2013.04.004
  10. Lee HJ, Oh TH, Yoon WJ, Kang GJ, Yang EJ, Park SS, et al. 2008. Eutigoside C inhibits the production of inflammatory mediators (NO, PGE2, IL-6) by down-regulating NF-${\kappa}B$ and MAP kinase activity in LPS-stimulated RAW 264.7 cells. J. Pharm. Pharmacol. 60: 917-924. https://doi.org/10.1211/jpp.60.7.0014
  11. Kim JB, Han AR, Park EY, Kim JY, Cho W, Lee J, et al. 2007. Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-${\kappa}B$ inactivation in RAW 264.7 macrophage cells. Biol. Pharm. Bull. 30: 2345-2351. https://doi.org/10.1248/bpb.30.2345
  12. Lawrence T. 2009. The nuclear factor NF-${\kappa}B$ pathway in inflammation. Cold Spring Harbor Perspect. Biol. 1: a001651. https://doi.org/10.1101/cshperspect.a001651
  13. Tak PP, Firestein GS. 2001. NF-${\kappa}B$: a key role in inflammatory diseases. J. Clin. Invest. 107: 7-11. https://doi.org/10.1172/JCI11830
  14. Yeom M, Kim JH, Min JH, Hwang MK, Jung HS, Sohn Y. 2015. Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-${\kappa}B$ and JNK/p38 MAPK. J. Ethnpharmacol. 24: 394-401.
  15. Fang H, Pengal RA, Cao X, Ganesan LP, Wewers MD, Marsh CB, et al. 2004. Lipopolysaccharide-induced macrophage inflammatory response is regulated by SHIP. J. Immunol. 173: 360-366. https://doi.org/10.4049/jimmunol.173.1.360
  16. Frazier WJ, Xue J, Luce WA, Liu Y. 2012. MAPK signaling drives inflammation in LPS-stimulated cardiomyocytes: the route of crosstalk to G-protein-coupled receptors. PLoS One. 7:e50071. https://doi.org/10.1371/journal.pone.0050071
  17. Neuder LE, Keener JM, Eckert RE, Trujillo JC, Jones SL. 2009. Role of p38 MAPK in LPS induced pro-inflammatory cytokine and chemokine gene expression in equine leukocytes. Vet. Immunol. Immunopathol. 294: 192-199.
  18. MacLeod AJ, Ross HB, Ozere RL, Digout G, van Rooyen CE. 1964. Lincomycin: A new antibiotic active against Staphylococci and other gram-positive cocci: Clinical and Laboratory Studies. Can. Med. Assoc. J. 14: 1056-1060.
  19. Duncan IB, Jeans B. 1965. Lincomycin in hospital practice. Can. Med. Assoc. J. 93 685-691.
  20. Imai Y, Sato S, Tanaka Y, Ochi K, Hosaka T. 2015. Lincomycin at subinhibitory concentrations potentiates secondary metabolite production by Streptomyces spp. Appl. Environ. Microbiol. 81: 3869-3879. https://doi.org/10.1128/AEM.04214-14
  21. Hall IH, Schwab UE, Ward ES, Ives TJ. 2003. Effects of moxifloxacin in zymogen A or S. aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection. Life Sci. 73: 2675-2685. https://doi.org/10.1016/S0024-3205(03)00611-8
  22. Nakano T, Hiramatsu K, Kishi K, Hirata N, Kadota J, Nasu M. 2003. Clindamycin modulates inflammatory-cytokine induction in lipopolysaccharide-stimulated mouse peritoneal macrophages. Antimicrob. Agents Chemother. 47: 363-367. https://doi.org/10.1128/AAC.47.1.363-367.2003
  23. Ulich TR, Yin S, Remick DG, Russell D, Eisenberg SP, Kohno T. 1993. Intratracheal administration of endotoxin and cytokines. IV. The soluble tumor necrosis factor receptor type I inhibits acute inflammation. Am. J. Pathol. 142: 1335-1338.
  24. Leigh WK, Firoz R, Richard DH, Jr., Rebecca CG, Suzanne MM. 1998. Effect of lipopolysaccharide and inflammatory cytokines on interleukin-6 production by healthy human gingival fibroblasts. Infect. Immun. 66: 608-614. https://doi.org/10.1128/IAI.66.2.608-614.1998
  25. Ramana KV, Fadl AA, Tammali R, Reddy AB, Chopra AK, Srivastava SK. 2006. Aldose reductase mediates the lipopolysa-ccharideinduced rele-ase of inflammatory mediators in RAW264.7 murine macrophages. J. Biol. Chem. 281: 33019-33029. https://doi.org/10.1074/jbc.M603819200
  26. Vo VA, Lee JW, Kim JY, Park JH, Lee HJ, Kim SS, et al. 2014. Phosphorylation of Akt mediates anti-Inflammatory activity of 1-p-Coumaroyl ${\beta}$-D-Glucoside against lipopolysaccharide-induced inflammation in RAW264.7 Cells. Korean J. Physiol Pharmacol. 18: 79-86. https://doi.org/10.4196/kjpp.2014.18.1.79
  27. Xu X, Li H, Hou X, Li D, He S, Wan C, et al. 2015. Punicalagin induces Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway and inhibits LPS-induced oxidative stress in RAW264.7 macrophages. Mediators Inflamm. 2015: 380218. https://doi.org/10.1155/2015/380218