Skip to main content
Log in

Suppressive functions of collismycin C in TGFBIp-mediated septic responses

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein; its expression by several cell types is greatly increased by TGF-β. TGFBIp is released by primary human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. 2,2′-Bipyridine-containing natural products are generally accepted to have antimicrobial, cytotoxic and anti-inflammatory properties. We hypothesized that a 2,2′-bipyridine containing natural product, collismycin C, could reduce TGFBIp-mediated severe inflammatory responses in human endothelial cells and mice. Here we investigated the effects and underlying mechanisms of collismycin C against TGFBIp-mediated septic responses. Collismycin C effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. In addition, collismycin C suppressed TGFBIp-induced sepsis lethality and pulmonary injury. This suppression of TGFBIp-mediated and CLP-induced septic responses indicates that collismycin C is a potential therapeutic agent for various severe vascular inflammatory diseases, with inhibition of the TGFBIp signaling pathway as the mechanism of action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Skonier J, Neubauer M, Madisen L, Bennett K, Plowman GD, Purchio AF (1992) cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor-beta. DNA Cell Biol 11:511–522

    PubMed  CAS  Google Scholar 

  2. Skonier J, Bennett K, Rothwell V, Kosowski S, Plowman G, Wallace P, Edelhoff S, Disteche C, Neubauer M, Marquardt H et al (1994) beta ig-h3: a transforming growth factor-beta-responsive gene encoding a secreted protein that inhibits cell attachment in vitro and suppresses the growth of CHO cells in nude mice. DNA Cell Biol 13:571–584

    PubMed  CAS  Google Scholar 

  3. Bae JS, Lee SH, Kim JE, Choi JY, Park RW, Yong Park J, Park HS, Sohn YS, Lee DS, Bae Lee E, Kim IS (2002) Betaig-h3 supports keratinocyte adhesion, migration, and proliferation through alpha3beta1 integrin. Biochem Biophys Res Commun 294:940–948

    PubMed  CAS  Google Scholar 

  4. Kim JE, Kim SJ, Jeong HW, Lee BH, Choi JY, Park RW, Park JY, Kim IS (2003) RGD peptides released from beta ig-h3, a TGF-beta-induced cell-adhesive molecule, mediate apoptosis. Oncogene 22:2045–2053

    PubMed  CAS  Google Scholar 

  5. Bae JS, Lee W, Son HN, Lee YM, Kim IS (2014) Anti-transforming growth factor beta-induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis. Acta Physiol (Oxf) 212:306–315

    CAS  Google Scholar 

  6. Bae JS, Lee W, Nam JO, Kim JE, Kim SW, Kim IS (2014) Transforming growth factor beta-induced protein promotes severe vascular inflammatory responses. Am J Respir Crit Care Med 189:779–786

    PubMed  Google Scholar 

  7. Gomi S, Amano S, Sato E, Miyadoh S, Kodama Y (1994) Novel antibiotics SF2738A, SF2738B and SF2738C, and their analogs produced by Streptomyces sp. J Antibiot (Tokyo) 47:1385–1394

    CAS  Google Scholar 

  8. Funk A, Divekar PV (1959) Caerulomycin, a new antibiotic from Streptomyces caeruleus Baldacci. I. Production, isolation, assay, and biological properties. Can J Microbiol 5:317–321

    PubMed  CAS  Google Scholar 

  9. Shindo K, Yamagishi Y, Okada Y, Kawai H (1994) Collismycins A and B, novel non-steroidal inhibitors of dexamethasone-glucocorticoid receptor binding. J Antibiot (Tokyo) 47:1072–1074

    CAS  Google Scholar 

  10. Tsuge N, Furihata K, Shin-Ya K, Hayakawa Y, Seto H (1999) Novel antibiotics pyrisulfoxin A and B produced by Streptomyces californicus. J Antibiot (Tokyo) 52:505–507

    CAS  Google Scholar 

  11. McInnes AG, Smith DG, Wright JLC, Vining LC (2011) Caerulomycins B and C, new 2,2′-dipyridyl derivatives from Streptomyces caeruleus. Can J Chem 55:4159–4165

    Google Scholar 

  12. Fu P, Wang S, Hong K, Li X, Liu P, Wang Y, Zhu W (2011) Cytotoxic bipyridines from the marine-derived actinomycete Actinoalloteichus cyanogriseus WH1-2216-6. J Nat Prod 74:1751–1756

    PubMed  CAS  Google Scholar 

  13. Kujur W, Gurram RK, Haleem N, Maurya SK, Agrewala JN (2015) Caerulomycin A inhibits Th2 cell activity: a possible role in the management of asthma. Sci Rep 5:15396

    PubMed  PubMed Central  CAS  Google Scholar 

  14. Kujur W, Gurram RK, Maurya SK, Nadeem S, Chodisetti SB, Khan N, Agrewala JN (2017) Caerulomycin A suppresses the differentiation of naive T cells and alleviates the symptoms of experimental autoimmune encephalomyelitis. Autoimmunity 50:317–328

    PubMed  CAS  Google Scholar 

  15. Lee IC, Bae JS (2017) Antiseptic effects of dabrafenib on TGFBIp-induced septic responses. Chem Biol Interact 278:92–100

    PubMed  CAS  Google Scholar 

  16. Buras JA, Holzmann B, Sitkovsky M (2005) Animal models of sepsis: setting the stage. Nat Rev Drug Discov 4:854–865

    PubMed  CAS  Google Scholar 

  17. Diehl KH, Hull R, Morton D, Pfister R, Rabemampianina Y, Smith D, Vidal JM, van de Vorstenbosch C (2001) A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 21:15–23

    PubMed  CAS  Google Scholar 

  18. Lee IC, Bae JS (2017) Suppressive effects of Sulforaphane on TGFBIp-mediated Sepsis. Nat Prod Commun 12:1627–1630

    Google Scholar 

  19. Min G, Ku SK, Lee T, Bae JS (2018) Suppressive effects of zingerone on TGFBIp-mediated septic responses. Arch Pharm Res 41:276–287

    PubMed  CAS  Google Scholar 

  20. Qin YH, Dai SM, Tang GS, Zhang J, Ren D, Wang ZW, Shen Q (2009) HMGB1 enhances the proinflammatory activity of lipopolysaccharide by promoting the phosphorylation of MAPK p38 through receptor for advanced glycation end products. J Immunol 183:6244–6250

    PubMed  CAS  Google Scholar 

  21. Sun C, Liang C, Ren Y, Zhen Y, He Z, Wang H, Tan H, Pan X, Wu Z (2009) Advanced glycation end products depress function of endothelial progenitor cells via p38 and ERK 1/2 mitogen-activated protein kinase pathways. Basic Res Cardiol 104:42–49

    PubMed  CAS  Google Scholar 

  22. Mittelstadt PR, Salvador JM, Fornace AJ Jr, Ashwell JD (2005) Activating p38 MAPK: new tricks for an old kinase. Cell Cycle 4:1189–1192

    PubMed  CAS  Google Scholar 

  23. Walton KL, Holt L, Sartor RB (2009) Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways. Am J Physiol Gastrointest Liver Physiol 296:G601–611

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Bae JS (2012) Role of high mobility group box 1 in inflammatory disease: Focus on sepsis. Arch Pharm Res 35:1511–1523

    PubMed  CAS  Google Scholar 

  25. Lee SH, Bae JS, Park SH, Lee BH, Park RW, Choi JY, Park JY, Ha SW, Kim YL, Kwon TH, Kim IS (2003) Expression of TGF-beta-induced matrix protein betaig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose. Kidney Int 64:1012–1021

    PubMed  CAS  Google Scholar 

  26. Park SW, Bae JS, Kim KS, Park SH, Lee BH, Choi JY, Park JY, Ha SW, Kim YL, Kwon TH, Kim IS, Park RW (2004) Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with alpha3beta1 integrin. Exp Mol Med 36:211–219

    PubMed  CAS  Google Scholar 

  27. Lin WN, Luo SF, Wu CB, Lin CC, Yang CM (2008) Lipopolysaccharide induces VCAM-1 expression and neutrophil adhesion to human tracheal smooth muscle cells: involvement of Src/EGFR/PI3-K/Akt pathway. Toxicol Appl Pharmacol 228:256–268

    PubMed  CAS  Google Scholar 

  28. Ruiz-Torres MP, Perez-Rivero G, Rodriguez-Puyol M, Rodriguez-Puyol D, Diez-Marques ML (2006) The leukocyte-endothelial cell interactions are modulated by extracellular matrix proteins. Cell Physiol Biochem 17:221–232

    PubMed  CAS  Google Scholar 

  29. Jung B, Ku SK, Gao M, Kim KM, Han MS, Choi H, Bae JS (2016) Suppressive effects of three diketopiperazines from marine-derived bacteria on TGFBIp-mediated septic responses in human endothelial cells and mice. Arch Pharm Res 39:843–854

    PubMed  CAS  Google Scholar 

  30. Jung B, Ku SK, Bae JS (2015) Ameliorative effect of methylthiouracil on TGFBIp-induced septic responses. Biochem Biophys Res Commun 463:661–666

    PubMed  CAS  Google Scholar 

  31. Lu N, Malemud CJ (2019) Extracellular signal-regulated kinase: a regulator of cell growth, inflammation, chondrocyte and bone cell receptor-mediated gene expression. Int J Mol Sci 20:3792

    PubMed Central  Google Scholar 

  32. Cohen J (2002) The immunopathogenesis of sepsis. Nature 420:885–891

    PubMed  CAS  Google Scholar 

  33. Su G, Atakilit A, Li JT, Wu N, Luong J, Chen R, Bhattacharya M, Sheppard D (2013) Effective treatment of mouse sepsis with an inhibitory antibody targeting integrin alphavbeta5*. Crit Care Med 41:546–553

    PubMed  CAS  Google Scholar 

  34. Su G, Hodnett M, Wu N, Atakilit A, Kosinski C, Godzich M, Huang XZ, Kim JK, Frank JA, Matthay MA, Sheppard D, Pittet JF (2007) Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function. Am J Respir Cell Mol Biol 36:377–386

    PubMed  CAS  Google Scholar 

  35. Kim JE, Jeong HW, Nam JO, Lee BH, Choi JY, Park RW, Park JY, Kim IS (2002) Identification of motifs in the fasciclin domains of the transforming growth factor-beta-induced matrix protein betaig-h3 that interact with the alphavbeta5 integrin. J Biol Chem 277:46159–46165

    PubMed  CAS  Google Scholar 

  36. Lee BH, Bae JS, Park RW, Kim JE, Park JY, Kim IS (2006) betaig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through alphavbeta5 integrin. Exp Mol Med 38:153–161

    PubMed  CAS  Google Scholar 

  37. Lee KH (2000) Research and future trends in the pharmaceutical development of medicinal herbs from Chinese medicine. Public Health Nutr 3:515–522

    PubMed  CAS  Google Scholar 

  38. Ku SK, Jeong SY, Yang S, Kim KM, Choi H, Bae JS (2019) Suppressive effects of collismycin C on polyphosphate-mediated vascular inflammatory responses. Fitoterapia 134:447–453

    PubMed  CAS  Google Scholar 

  39. Choi H, Lee W, Kim E, Ku SK, Bae JS (2019) Inhibitory effects of collismycin C and pyrisulfoxin A on particulate matter-induced pulmonary injury. Phytomedicine 62:152939

    PubMed  CAS  Google Scholar 

  40. Lee JH, Kim E, Choi H, Lee J (2017) Collismycin C from the micronesian marine bacterium Streptomyces sp. MC025 inhibits Staphylococcus aureus biofilm formation. Mar Drugs 15:387

    PubMed Central  Google Scholar 

  41. Kim JE, Lee W, Yang S, Cho SH, Baek MC, Song GY, Bae JS (2019) Suppressive effects of rare ginsenosides, Rk1 and Rg5, on HMGB1-mediated septic responses. Food Chem Toxicol 124:45–53

    PubMed  CAS  Google Scholar 

  42. Lee BS, Lee C, Yang S, Ku SK, Bae JS (2019) Renal protective effects of zingerone in a mouse model of sepsis. BMB Rep 52:271–276

    PubMed  PubMed Central  CAS  Google Scholar 

  43. Lee IC, Bae JS (2019) Pelargonidin protects against renal injury in a mouse model of sepsis. J Med Food 22:57–61

    PubMed  CAS  Google Scholar 

  44. Carbone L, Carbone ET, Yi EM, Bauer DB, Lindstrom KA, Parker JM, Austin JA, Seo Y, Gandhi AD, Wilkerson JD (2012) Assessing cervical dislocation as a humane euthanasia method in mice. J Am Assoc Lab Anim Sci JAALAS 51:352–356

    PubMed  CAS  Google Scholar 

  45. Lee W, Ku SK, Kim JE, Cho GE, Song GY, Bae JS (2019) Pulmonary protective functions of rare ginsenoside Rg4 on particulate matter-induced inflammatory responses. Biotechnol Bioprocess Eng 24:445–453

    CAS  Google Scholar 

  46. Lee Y, Jeong MH, Kim KJ, Baek SH, Hur JS, Son YJ (2018) The extract of Ramalina litoralis inhibits osteoclast differentiation. Biotechnol Bioprocess Eng 23:634–640

    CAS  Google Scholar 

  47. Ozdulger A, Cinel I, Koksel O, Cinel L, Avlan D, Unlu A, Okcu H, Dikmengil M, Oral U (2003) The protective effect of N-acetylcysteine on apoptotic lung injury in cecal ligation and puncture-induced sepsis model. Shock 19:366–372

    PubMed  CAS  Google Scholar 

  48. Mackman N, Brand K, Edgington TS (1991) Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites. J Exp Med 174:1517–1526

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by Kyungpook National University Development Project Research Fund, 2018.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hyukjae Choi or Jong-Sup Bae.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 261 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, BS., Kim, E., Choi, H. et al. Suppressive functions of collismycin C in TGFBIp-mediated septic responses. J Nat Med 74, 387–398 (2020). https://doi.org/10.1007/s11418-019-01374-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-019-01374-9

Keywords

Navigation