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Microbiology and Biotechnology Letters

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Molecular and Cellular Microbiology / Biomedical Sciences  |  Clinical Microbiology and Biomedical Sciences

Microbiol. Biotechnol. Lett. 2020; 48(3): 366-372

https://doi.org/10.4014/mbl.2002.02015

Received: February 20, 2020; Accepted: March 24, 2020

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

Eun-Jin Yang , Nari Lee and Chang-Gu Hyun *

Department of Chemistry and Cosmetics, Jeju National University, Jeju, Republic of Korea

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: Lincomycin, antibiotic, inflammatory, nitric oxide, RAW 264.7

  1. Udommethaporn S, Tencomnao T, McGowan EM, Boonyaratanakornkit V. 2016. Assessment of anti-TNF-α activities in keratinocytes expressing inducible TNF- α: A novel tool for anti-TNF-α drug screening. PLoS One 11: e0159151.
    Pubmed KoreaMed CrossRef
  2. Lapara NJ 3rd, Kelly BL. 2010. Suppression of LPS-induced inflammatory responses in acrophages infected with Leishmania. J. Inflamm (Lond). 7: 8.
    Pubmed KoreaMed CrossRef
  3. Zhang X, Li N, Shao H, Meng Y, Wang L, Wu Q, et al. 2016. Methane limit LPS-induced NF-κB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3βmediated IL-10 expression. Sci. Rep. 11: 6.
    Pubmed KoreaMed CrossRef
  4. Gao HM, Liu B, Zhang W, Hong JS. 2003. Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol. Sci. 24: 395401.
    CrossRef
  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.
    Pubmed KoreaMed CrossRef
  6. Roos-Engstrand E, Wallin A, Bucht A, Pourazar J, Sandström T, Blomberg A. 2005. Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure. Eur. Respir. J. 25: 797-803.
    Pubmed CrossRef
  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.
    Pubmed KoreaMed CrossRef
  8. Yang G, Lee K, Lee M, Ham I, Choi HY. 2012. Inhibition of lipopolysaccharideinduced nitric oxide and prostaglandin E2 production by chlo-roform fraction of Cudrania tricuspidata in RAW 264.7 macrophages. BMC Complement. Altern. Med. 12: 250.
    Pubmed KoreaMed CrossRef
  9. Gomez I, Foudi N, Longrois D, Norel X. 2013. The role of prostaglandin E2 in human vascular inflammation. Prostaglandins Leukot. Essent. Fatty Acids 89: 55-63.
    Pubmed CrossRef
  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-κB and MAP kinase activity in LPS-stimulated RAW 264.7 cells. J. Pharm. Pharmacol. 60:917-924.
    Pubmed CrossRef
  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-κB inactivation in RAW 264.7 macrophage cells. Biol. Pharm. Bull. 30: 2345-2351.
    Pubmed CrossRef
  12. Lawrence T. 2009. The nuclear factor NF-κB pathway in inflammation. Cold Spring Harbor Perspect. Biol. 1: a001651.
    Pubmed KoreaMed CrossRef
  13. Tak PP, Firestein GS. 2001. NF-κB: a key role in inflammatory diseases. J. Clin. Invest. 107: 7-11.
    Pubmed KoreaMed CrossRef
  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-κB and JNK/p38 MAPK. J. Ethnpharmacol. 24: 394-401.
    Pubmed CrossRef
  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.
    Pubmed CrossRef
  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.
    Pubmed KoreaMed CrossRef
  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.
    Pubmed CrossRef
  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.
    Pubmed KoreaMed CrossRef
  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.
    CrossRef
  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
    Pubmed KoreaMed CrossRef
  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.
    Pubmed KoreaMed CrossRef
  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.
    Pubmed CrossRef
  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-pCoumaroyl β-D-Glucoside against lipopolysaccharide-induced inflammation in RAW264.7 Cells. Korean J. Physiol Pharmacol. 18:79-86.
    Pubmed KoreaMed CrossRef
  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.
    Pubmed KoreaMed CrossRef

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