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TIP Revista Especializada en Ciencias Químico-Biológicas

2022, Número 1

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TIP Rev Esp Cienc Quim Biol 2022; 25 (1)


La exposición al extracto del humo del cigarro induce la proliferación y la sobreexpresión de CCL2 en células A549, así como la migración de fibroblastos pulmonares

García-Trejo SS, Medina-Pérez DM, Balderas-Martínez YI

Idioma: Español
Referencias bibliográficas: 45
Paginas: 1-12
Archivo PDF: 627.79 Kb.


RESUMEN

La Fibrosis Pulmonar Idiopática (FPI) es una enfermedad en la que el hábito al tabaco es el principal factor de riesgo, presenta un proceso de remodelado complejo y desregulado en la que el sistema inmune tiene un papel importante. El extracto del humo del cigarro (CSE) es dañino y da lugar a la síntesis de citocinas en el epitelio del tracto respiratorio. La quimiocina CCL2, se encuentra, por lo general, elevada en lavado broncoalveolar de pacientes con FPI. Sin embargo, se desconoce si el CSE induce su efecto profibrótico a través de CCL2. El objetivo de este estudio fue evaluar el rol de CCL2 en la migración y expresión de moléculas profibróticas al usar un modelo in vitro de células epiteliales pulmonares A549 transfectadas con el gen de CCL2 y los fibroblastos CCD25 estimulados con el CSE. Los resultados indican que el CSE incrementa la expresión de CCL2, y modula la migración y proliferación de las células A549, así como la expresión y síntesis de TGF-β1. El medio condicionado proveniente de las células A549 que sobreexpresan a CCL2 induce a la migración y a la sobreexpresión del gen IL6 en los fibroblastos. Así mismo, la sobreexpresión de CCL2 en las células A549 estimuladas con el CSE da lugar a un efecto profibrótico en células CCD25, fungiendo como un orquestador en el desarrollo de la FPI.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Agostini, C. & Gurrieri, C. (2006). Chemokine / CytokineCocktail in Idiopathic Pulmonary Fibrosis. Proc. Am.Thorac. Soc., 3(4), 357–363. https://doi.org/10.1513/pats.200601-010TK

  2. Antoniades, H. N., Neville-Golden, J., Galanopoulos, T.,Kradin, R. L., Valente, A. J. & Graves, D. T. (1992).Expression of monocyte chemoattractant protein 1 mRNAin human idiopathic pulmonary fibrosis. Proc. Natl. Acad.Sci. U S A, 89(12), 5371–5375. https://doi.org/10.1073/pnas.89.12.5371

  3. Binder, N. B., Niederreiter, B., Hoffmann, O., Stange, R.,Pap, T., Stulnig, T. M., MacK, M., Erben, R. G., Smolen,J. S. & Redlich, K. (2009). Estrogen-dependent and C-Cchemokine receptor-2-dependent pathways determineosteoclast behavior in osteoporosis. Nat. Med., 15(4), 417–42

  4. https://doi.org/10.1038/nm.19454. Checa, M., Hagood, J. S., Velazquez-Cruz, R., Ruiz, V., Garcia-De-Alba, C., Rangel-Escareño, C., Urrea, F., Becerril, C.,Montaño, M., Garcia-Trejo, S., Cisneros Lira, J., Aquino-Gálvez, A., Pardo, A. & Selman, M. (2016). Cigarettesmoke enhances the expression of profibrotic molecules inalveolar epithelial cells. PLoS ONE, 11(3), 1–19. https://doi.org/10.1371/journal.pone.0150383

  5. Chen, Gao, Han, Pan, C. (2015). The CCL2 / CCR2 axisenhances IL-6-induced epithelial-mesenchymal transitionby cooperatively activating STAT3-Twist signaling. TumorBiol., 36(2), 973–981. https://doi.org/10.1007/s13277-014-2717-z

  6. Chompre, G., Martinez-Orengo, N., Cruz, M., Porter, J. T.& Noel, R. J. (2019). TGFβRI antagonist inhibits HIV-1Nef-induced CC chemokine family ligand 2 (CCL2) in thebrain and prevents spatial learning impairment. Journal ofNeuroinflammation, 16(1), 1–19. https://doi.org/10.1186/s12974-019-1664-4

  7. Deng, X., Xu, M., Yuan, C., Yin, L., Chen, X., Zhou, X., Li,G., Fu, Y., Feghali-Bostwick, C. A. & Pang, L. (2013).Transcriptional regulation of increased CCL2 expression inpulmonary fibrosis involves nuclear factor-kB and activatorprotein-1. Int. J. Biochem. Cell Biol., 45(7), 1366–1376.https://doi.org/10.1016/j.biocel.2013.04.003

  8. Ekert, J. E., Murray, L. A., Das, A. M., Sheng, H., Giles-Komar,J. & Rycyzyn, M. A. (2011). Chemokine (C-C motif) ligand2 mediates direct and indirect fibrotic responses in humanand murine cultured fibrocytes. Fibrogenesis & TissueRepair, 4(1), 23. https://doi.org/10.1186/1755-1536-4-23

  9. Gharaee-Kermani, M., Denholm, E. M. & Phan, S. H. (1996).Costimulation of Fibroblast Collagen and TransformingGrowth Factor 1 Gene Expression by MonocyteChemoattractant Protein-1 via Specific Receptors. J. Biol.Chem., 271(30), 17779–17784. https://doi.org/10.1074/jbc.271.30.17779

  10. Grada, A., Otero-Vinas, M., Prieto-Castrillo, F., Obagi, Z. &Falanga, V. (2017). Research Techniques Made Simple:Analysis of Collective Cell Migration Using the WoundHealing Assay. Journal of Investigative Dermatology,137(2), e11–e16. https://doi.org/10.1016/j.jid.2016.11.020

  11. Heinrich, P. C., Behrmann, I., Haan, S., Hermanns, H. M.,Müller-Newen, G. & Schaper, F. (2003). Principlesof interleukin (IL)-6-type cytokine signalling and itsregulation. The Biochemical Journal, 374(Pt 1), 1–20.https://doi.org/10.1042/BJ20030407

  12. Hinojosa, A. E., Garcia-Bueno, B., Leza, J. C. & Madrigal, J. L.(2011). CCL2 / MCP-1 modulation of microglial activationand proliferation. J. Neuroinflammation, 8(1), 77. https://doi.org/10.1186/1742-2094-8-77

  13. Inoshima, I., Kuwano, K., Hamada, N., Hagimoto, N., Yoshimi,M., Maeyama, T., Takeshita, A., Kitamoto, S., Egashira,K. & Hara, N. (2004). Anti-monocyte chemoattractantprotein-1 gene therapy attenuates pulmonary fibrosis inmice. American Journal of Physiology - Lung Cellularand Molecular Physiology, 286(5), L1038-44. https://doi.org/10.1152/ajplung.00167.2003

  14. Iyonaga, K., Takeya, M., Saita, N., Sakamoto, O., Yoshimura,T., Ando, M. & Takahashi, K. (1994). Monocytechemoattractant protein-1 in idiopathic pulmonaryfibrosis and other interstitial lung diseases. Hum.Pathol., 25(5), 455–463. https://doi.org/10.1016/0046-8177(94)90117-1

  15. Kim, K. K., Kugler, M. C., Wolters, P. J., Robillard, L., Galvez, M.G., Brumwell, A. N., Sheppard, D. & Chapman, H. A. (2006).Alveolar epithelial cell mesenchymal transition developsin vivo during pulmonary fibrosis and is regulated by theextracellular matrix. Proceedings of the National Academyof Sciences of the United States of America, 103(35),13180–13185. https://doi.org/10.1073/pnas.0605669103

  16. King, T. E., Pardo, A. & Selman, M. (2011). Idiopathic pulmonaryfibrosis. The Lancet, 378(9807), 1949–1961. https://doi.org/10.1016/S0140-6736(11)60052-4 King, T. E., Schwarz, M. I., Brown, K., Tooze, J. A., Colby, T.V., Waldron, J. A., Flint, A., Thurlbeck, W. & Cherniack,R. M. (2001). Idiopathic pulmonary fibrosis: Relationshipbetween histopathologic features and mortality. Am. J.Respir. Crit. Care Med., 164(6), 1025–1032. https://doi.org/10.1164/ajrccm.164.6.2001056

  17. Kuhn, C. & Mcdonald, J. A. (1991). The Roles of theMyofibroblast in Idiopathic Pulmonary FibrosisUltrastructural and Immunohistochemical Features of Sitesof Active Extracellular Matrix Synthesis. Am. J. Pathol.,138(5), 1257–1265.

  18. Liu, X., Das, A. M., Seideman, J., Griswold, D., Afuh, C. N.,Kobayashi, T., Abe, S., Fang, Q., Hashimoto, M., Kim, H.,Wang, X., Shen, L., Kawasaki, S. & Rennard, S. I. (2007).The CC chemokine ligand 2 (CCL2) mediates fibroblastsurvival through IL-6. American Journal of RespiratoryCell and Molecular Biology, 37(1), 121–128. https://doi.org/10.1165/rcmb.2005-0253OC

  19. Liu, Y., Gao, W. & Zhang, D. (2010). Effects of cigarette smokeextract on A549 cells and human lung fibroblasts treatedwith transforming growth factor-beta1 in a coculture system.Clin. Exp. Med., 10(3), 159–167. https://doi.org/10.1007/s10238-009-0081-x

  20. Loberg, R. D., Day, L. L., Harwood, J., Ying, C., St. John, L.N., Giles, R., Neeley, C. K. & Pienta, K. J. (2006). CCL2is a Potent Regulator of Prostate Cancer Cell Migrationand Proliferation. Neoplasia, 8(7), 578–586. https://doi.org/10.1593/neo.06280

  21. Louis, K. S. & Siegel, A. C. (2011). Cell Viability AnalysisUsing Trypan Blue: Manual and Automated Methods. InM. J. Stoddart (Ed.), Mammalian Cell Viability. Methods inmolecular biology (Vol. 740, Issue 1, pp. 7–12). HumanaPress. https://doi.org/10.1007/978-1-61779-108-6

  22. Mercer, P. F., Johns, R. H., Scotton, C. J., Krupiczojc, M. A.,Königshoff, M., Howell, D. C. J., McAnulty, R. J., Das, A.,Thorley, A. J., Tetley, T. D., Eickelberg, O. & Chambers,R. C. (2009). Pulmonary Epithelium Is a Prominent Sourceof Proteinase-activated Receptor-1–inducible CCL2 inPulmonary Fibrosis. American Journal of Respiratoryand Critical Care Medicine, 179(5), 414–425. https://doi.org/10.1164/rccm.200712-1827OC

  23. Moodley, Y. P., Misso, N. L. A., Scaffidi, A. K., Fogel-Petrovic,M., McAnulty, R. J., Laurent, G. J., Thompson, P. J. &Knight, D. A. (2003). Inverse Effects of Interleukin-6on Apoptosis of Fibroblasts from Pulmonary Fibrosisand Normal Lungs. Am. J. Respir. Cell Mol. Biol., 29(4),490–498. https://doi.org/10.1165/rcmb.2002-0262OC

  24. Murray, L., Argentieri, R., Farrell, F., Bracht, M., Sheng, H.,Whitaker, B., Beck, H., Tsui, P., Cochlin, K., Evanoff, H.,Hogaboam, C. & Das, A. (2008). Hyper-responsivenessof IPF/UIP fibroblasts: Interplay between TGFβ1, IL-13and CCL2. Int. J. Biochem. Cell Biol., 40(10), 2174–2182.https://doi.org/10.1016/j.biocel.2008.02.016

  25. Nakatsumi, H., Matsumoto, M. & Nakayama, K. I. (2017).Noncanonical Pathway for Regulation of CCL2 Expressionby an mTORC1-FOXK1 Axis Promotes Recruitmentof Tumor-Associated Macrophages. Cell Rep., 21(9),2471–2486. https://doi.org/10.1016/j.celrep.2017.11.014

  26. Nielsen, S. H., Willumsen, N., Leeming, D. J., Daniels, S. J.,Brix, S. & Karsdal, M. A. (2019). Serological Assessmentof Activated Fibroblasts by alpha- Smooth Muscle Actin ( α-SMA ): A Noninvasive Biomarker of Activated Fibroblastsin Lung. Transl. Oncol., 12(2), 368–374. https://doi.org/10.1016/j.tranon.2018.11.004

  27. Oldham, M. J., DeSoi, D. J., Rimmer, L. T., Wagner, K. A. &Morton, M. J. (2014). Insights from analysis for harmfuland potentially harmful constituents (HPHCs) in tobaccoproducts. Regulatory Toxicology and Pharmacology, 70(1),138–148. https://doi.org/10.1016/j.yrtph.2014.06.017

  28. Paccosi, S., Giachi, M., Di, P., Guglielmotti, A. & Parenti,A. (2016). Cytokine The chemokine ( C-C motif ) ligandprotein synthesis inhibitor bindarit prevents cytoskeletalrearrangement and contraction of human mesangialcells. Cytokine, 85, 92–100. https://doi.org/10.1016/j.cyto.2016.06.012

  29. Raghu, G., Collard, H. R., Egan, J. J., Martinez, F. J., Behr, J.,Brown, K. K., Colby, T. V., Cordier, J. F., Flaherty, K. R.,Lasky, J. A., Lynch, D. A., Ryu, J. H., Swigris, J. J., Wells,A. U., Ancochea, J., Bouros, D., Carvalho, C., Costabel, U.,Ebina, M., Hansell D., Johko T., Kim D., King T., KondohY., Myers J., Muller N., Nicholson A., Richeldi L., SelmanM., Dudden R., Griss B., Protzco S. & Schünemann, H.J. (2011). An Official ATS/ERS/JRS/ALAT Statement:Idiopathic pulmonary fibrosis: Evidence-based guidelinesfor diagnosis and management. American Journal ofRespiratory and Critical Care Medicine, 183(6), 788–824.https://doi.org/10.1164/rccm.2009-040GL

  30. Raghu, G., Martinez, F. J., Brown, K. K., Costabel, U., Cottin,V., Wells, A. U., Lancaster, L., Gibson, K. F., Haddad, T.,Agarwal, P., Mack, M., Dasgupta, B., Nnane, I. P., Flavin,S. K. & Barnathan, E. S. (2015). CC-chemokine ligand 2inhibition in idiopathic pulmonary fibrosis: A phase 2 trialof carlumab. Eur. Respir. J., 46(6), 1740–1750. https://doi.org/10.1183/13993003.01558-2014

  31. Roca, H., Varcos, Z. S., Sud, S., Craig, M. J. & Pienta, K. J.(2009). CCL2 and interleukin-6 promote survival of humanCD11b+ peripheral blood mononuclear cells and induceM2-type macrophage polarization. J. Biol. Chem., 284(49),34342–34354. https://doi.org/10.1074/jbc.M109.042671

  32. Rose, C. E., Sung, S.-S. J. & Fu, S. M. (2010). SignificantInvolvement of CCL2 (MCP-1) in Inflammatory Disordersof the Lung. Microcirculation, 10(3–4), 273–288. https://doi.org/10.1038/sj.mn.7800193

  33. Ruigrok, M. J. R., Frijlink, H. W., Melgert, B. N., Olinga, P.& Hinrichs, W. L. J. (2021). Gene therapy strategies foridiopathic pulmonary fibrosis: recent advances, currentchallenges, and future directions. Molecular Therapy -Methods and Clinical Development, 20(March), 483–496.https://doi.org/10.1016/j.omtm.2021.01.003

  34. Selman, M. & Pardo, A. (2020). The leading role of epithelialcells in the pathogenesis of idiopathic pulmonary fibrosis.Cell Signal, 66, 109482. https://doi.org/10.1016/j.cellsig.2019.109482

  35. Sgalla, G., Flore, M., Siciliano, M., Richeldi, L., Sgalla, G.,Flore, M., Siciliano, M. & Richeldi, L. (2020). Antibodybasedtherapies for idiopathic pulmonary fibrosis. Expert.Opin. Biol. Ther., 20(7), 779–786. https://doi.org/10.1080/14712598.2020.1735346

  36. Shiraishi, K., Shichino, S., Ueha, S., Nakajima, T. & Hashimoto,S. (2019). Mesenchymal-Epithelial Interactome AnalysisReveals Essential Factors Required for Fibroblast- FreeAlveolosphere Formation. IScience, 11, 318–333. https://doi.org/10.1016/j.isci.2018.12.022

  37. Stainer, A., Faverio, P., Busnelli, S., Catalano, M., Zoppa,M. Della, Marruchella, A., Pesci, A. & Luppi, F. (2021).Molecular biomarkers in idiopathic pulmonary fibrosis:State of the art and future directions. International Journalof Molecular Sciences, 22(12). https://doi.org/10.3390/ijms22126255

  38. Tang, C. H. & Tsai, C. C. (2012). CCL2 increases MMP-9expression and cell motility in human chondrosarcomacells via the Ras/Raf/MEK/ERK/NF-κB signalingpathway. Biochem. Pharmacol., 83(3), 335–344. https://doi.org/10.1016/j.bcp.2011.11.013

  39. Van Der Poel, H. . (2004). Mammalian target of rapamycinand 3-phosphatidylinositol 3-kinase pathway inhibitionenhances growth inhibition of transforming growthfactor-b1 in prostate cancer cells. The Journal of Urology,172(October), 1333–1337. https://doi.org/10.1097/01.ju.0000138829.97838.19

  40. Van Geffen, C., Deibler, A., Quante, M., Renz, H., Hartl,D. & Kolahian, S. (2021). Regulatory Immune Cells inIdiopathic Pulmonary Fibrosis: Friends or Foes? Frontiersin Immunology, 12(April), 1–18. https://doi.org/10.3389/fimmu.2021.663203

  41. Viedt, C., Dechend, R., Fei, J., Hänsch, G. M., Kreuzer, J. &Orth, S. R. (2002). MCP-1 induces inflammatory activationof human tubular epithelial cells: Involvement of thetranscription factors, nuclear factor-κB and activatingprotein-1. J. Am. Soc. Nephrol., 13(6), 1534–1547. https://doi.org/10.1097/01.ASN.0000015609.31253.7F

  42. Xue, M., Guo, Z., Cai, C., Sun, B. & Wang, H. (2019). Evaluationof the Diagnostic Efficacies of Serological Markers KL-6,SP-A, SP-D, CCL2, and CXCL13 in Idiopathic InterstitialPneumonia. Respiration, 98(6), 534–545. https://doi.org/10.1159/000503689

  43. Yang, J, Agarwal, M., Ling, S., Teitz-Tennenbaum, S., Zemans,R., Osterholzer, J., Sisson, T., Kim, K. & Kim, K. K. (2020).Diverse Injury Pathways Induce Alveolar Epithelial CellCCL2/12 Which Promotes Lung Fibrosis. Am. J. Respir.Cell Mol. Biol., 62(5), 622–632. https://doi.org/10.1165/rcmb.2019-0297oc

  44. Yang, Jibing, Wheeler, S. E., Velikoff, M., Kleaveland, K. R.,LaFemina, M. J., Frank, J. A., Chapman, H. A., Christensen,P. J. & Kim, K. K. (2013). Activated Alveolar EpithelialCells Initiate Fibrosis through Secretion of MesenchymalProteins. The American Journal of Pathology, 183(5),1559–1570. https://doi.org/10.1016/j.ajpath.2013.07.016

  45. Zoz, D. F., Lawson, W. E. & Blackwell, T. S. (2012). Idiopathicpulmonary fibrosis: a disorder of epithelial cell dysfunction.Am. J. Med. Sci., 341(6), 435–438. https://doi.org/10.1097/MAJ.0b013e31821a9d8e




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