Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines - PubMed (original) (raw)
. 2006 Feb 1;210(3):181-9.
doi: 10.1016/j.taap.2005.05.002. Epub 2005 Jun 17.
Affiliations
- PMID: 15964043
- DOI: 10.1016/j.taap.2005.05.002
Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines
Raymund R Razonable et al. Toxicol Appl Pharmacol. 2006.
Abstract
The clinical use of bleomycin results in systemic and pulmonary inflammatory syndromes that are mediated by the production of cytokines and chemokines. In this study, we demonstrate that cell activation is initiated upon the recognition of bleomycin as a pathogen-associated molecular pattern by toll-like receptor (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high levels of TLR2, secretes interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha during bleomycin exposure. The TLR2-dependent nature of cell activation and cytokine secretion is supported by (1) the inability of TLR2-deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa B (NF-kappaB) activation and secrete IL-8 in response to bleomycin; (2) the acquired ability of HEK293 to exhibit NF-kappaB activation and secrete IL-8 upon experimental expression of TLR2; and (3) the inhibition of cell activation in TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively, these observations identify TLR2 activation as a critical event that triggers NF-kappaB activation and secretion of cytokines and chemokines during bleomycin exposure. Our in vitro findings could serve as a molecular mechanism underlying the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin engages with other cellular receptors that results in activation of alternate signaling pathways and whether the TLR2-agonist activity of bleomycin contribute to its anti-neoplastic property deserve further study.
Similar articles
- Leptospiral membrane proteins stimulate pro-inflammatory chemokines secretion by renal tubule epithelial cells through toll-like receptor 2 and p38 mitogen activated protein kinase.
Hung CC, Chang CT, Tian YC, Wu MS, Yu CC, Pan MJ, Vandewalle A, Yang CW. Hung CC, et al. Nephrol Dial Transplant. 2006 Apr;21(4):898-910. doi: 10.1093/ndt/gfi316. Epub 2005 Dec 8. Nephrol Dial Transplant. 2006. PMID: 16339163 - Effects of ketamine on levels of cytokines, NF-kappaB and TLRs in rat intestine during CLP-induced sepsis.
Yu M, Shao D, Liu J, Zhu J, Zhang Z, Xu J. Yu M, et al. Int Immunopharmacol. 2007 Aug;7(8):1076-82. doi: 10.1016/j.intimp.2007.04.003. Epub 2007 May 2. Int Immunopharmacol. 2007. PMID: 17570324 - Systematic analysis highlights the key role of TLR2/NF-kappaB/MAP kinase signaling for IL-8 induction by macrophage-like THP-1 cells under influence of Borrelia burgdorferi lysates.
Sadik CD, Hunfeld KP, Bachmann M, Kraiczy P, Eberhardt W, Brade V, Pfeilschifter J, Mühl H. Sadik CD, et al. Int J Biochem Cell Biol. 2008;40(11):2508-21. doi: 10.1016/j.biocel.2008.04.014. Epub 2008 May 16. Int J Biochem Cell Biol. 2008. PMID: 18571457 - Synergism of toll-like receptor 2 (TLR2), TLR4, and TLR6 ligation on the production of tumor necrosis factor (TNF)-alpha in a spontaneous arthritis animal model of interleukin (IL)-1 receptor antagonist-deficient mice.
Jung YO, Cho ML, Lee SY, Oh HJ, Park JS, Park MK, Park MJ, Ju JH, Kim SI, Park SH, Kim HY, Min JK. Jung YO, et al. Immunol Lett. 2009 Apr 27;123(2):138-43. doi: 10.1016/j.imlet.2009.03.004. Epub 2009 Mar 21. Immunol Lett. 2009. PMID: 19428561
Cited by
- Bleomycin inhibits proliferation and induces apoptosis in TPC-1 cells through reversing M2-macrophages polarization.
Liu H, Dong H, Jiang L, Li Z, Ma X. Liu H, et al. Oncol Lett. 2018 Sep;16(3):3858-3866. doi: 10.3892/ol.2018.9103. Epub 2018 Jul 6. Oncol Lett. 2018. PMID: 30127999 Free PMC article. - TLR2 in pleural fluid is modulated by talc particles during pleurodesis.
Jankovicova K, Kondelkova K, Habal P, Andrys C, Krejsek J, Mandak J. Jankovicova K, et al. Clin Dev Immunol. 2012;2012:158287. doi: 10.1155/2012/158287. Epub 2012 Dec 10. Clin Dev Immunol. 2012. PMID: 23304186 Free PMC article. Clinical Trial. - Decreased pulmonary inflammation following ethanol and burn injury in mice deficient in TLR4 but not TLR2 signaling.
Bird MD, Zahs A, Deburghgraeve C, Ramirez L, Choudhry MA, Kovacs EJ. Bird MD, et al. Alcohol Clin Exp Res. 2010 Oct;34(10):1733-41. doi: 10.1111/j.1530-0277.2010.01260.x. Epub 2010 Jul 1. Alcohol Clin Exp Res. 2010. PMID: 20608903 Free PMC article. - Protective effect of hydroxysafflor yellow A on bleomycin- induced pulmonary inflammation and fibrosis in rats.
Jin M, Wang L, Wu Y, Zang BX, Tan L. Jin M, et al. Chin J Integr Med. 2018 Jan;24(1):32-39. doi: 10.1007/s11655-017-2094-z. Epub 2018 Jan 3. Chin J Integr Med. 2018. PMID: 29294256 - Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13.
Aliprantis AO, Wang J, Fathman JW, Lemaire R, Dorfman DM, Lafyatis R, Glimcher LH. Aliprantis AO, et al. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2827-30. doi: 10.1073/pnas.0700021104. Epub 2007 Feb 16. Proc Natl Acad Sci U S A. 2007. PMID: 17307869 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous