Immunomodulatory Activity of Diterpenes over Innate Immunity and Cytokine Production in a Human Alveolar Epithelial Cell Line Infected with Mycobacterium tuberculosis

Article ID: e051022209604 Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Mexico has the largest number of the genus salvia plant species, whose main chemical compounds of this genus are diterpenes, these chemical compounds have shown important biological activities such as: antimicrobial, anti-inflammatory and immunomodulatory.

Objective: This study aimed to evaluate the immunomodulatory activity of three diterpenes: 1) icetexone, 2) anastomosine and 3) 7,20-dihydroanastomosine, isolated from Salvia ballotiflora, over innate immunity and cytokine production in a human alveolar epithelial cell line infected with Mycobacterium tuberculosis.

Methods: The immunomodulatory activity of diterpenes over innate immunity included reactive oxygen and nitrogen species (ROS and RNS) induction in response to infection; cytokine production included TNF-α and TGF-β induction in response to infection.

Results: The diterpenes anastomosine and 7,20-dihydroanastomosine showed a statically significant (p < 0.01) increase of RNS after 36 h of infection and treatment of 2.0 μg/mL. Then, the ROS induction in response to infection showed a consistent statically significant (p < 0.01) increase after 12 h of diterpenes treatments. The cell cultures showed an anti-inflammatory effect, in the case of TGF-β induction, in response to infection when treated with the diterpenes. On the other hand, there was not any significant effect on TNF-α release.

Conclusion: The diterpenes anastomosine and 7,20-dihydroanastomosine increased the production of RNS after 36 h of infection and treatment. Besides, the three diterpenes increased the production of ROS after 12 h. This RNS and ROS modulation can be considered as an in vitro correlation of innate immunity in response to Mycobacterium tuberculosis infection; and an indicator of the damage of epithelial lung tissue. This study also showed an anti-inflammatory immune response by means of TGF-β modulation when compared with control group.

Keywords: Inmmunomodulatory activity, icetexone, anastomosine, 7, 20-dihydroanastomosine, innate immunity, chemokine production, mycobacterium tuberculosis, A549.

Graphical Abstract

[1]
Hunter, R.L. Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis. Tuberculosis, 2016, 97, 8-17.
[http://dx.doi.org/10.1016/j.tube.2015.11.010] [PMID: 26980490]
[2]
Pai, M.; Behr, M.A.; Dowdy, D.; Dheda, K.; Divangahi, M.; Boehme, C.C.; Ginsberg, A.; Swaminathan, S.; Spigelman, M.; Getahun, H.; Menzies, D.; Raviglione, M. Tuberculosis. Nat. Rev. Dis. Primers, 2016, 2(1), 16076.
[http://dx.doi.org/10.1038/nrdp.2016.76] [PMID: 27784885]
[3]
World Health Organization.Global Tuberculosis Report. Licence: CC BY-NC-SA 3.0 IGO. Geneva 2021. Available from: https://www.who.int/publications/i/item/9789240037021
[4]
Weiss, G.; Schaible, U.E. Macrophage defense mechanisms against intracellular bacteria. Immunol. Rev., 2015, 264(1), 182-203.
[http://dx.doi.org/10.1111/imr.12266] [PMID: 25703560]
[5]
Bell, L.C.K.; Noursadeghi, M. Pathogenesis of HIV-1 and Mycobacterium tuberculosis co-infection. Nat. Rev. Microbiol., 2018, 16(2), 80-90.
[http://dx.doi.org/10.1038/nrmicro.2017.128] [PMID: 29109555]
[6]
Cohen, S.B.; Gern, B.H.; Delahaye, J.L.; Adams, K.N.; Plumlee, C.R.; Winkler, J.K.; Sherman, D.R.; Gerner, M.Y.; Urdahl, K.B. Alveolar macrophages provide an early mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe, 2018, 24(3), 439-446.e4.
[http://dx.doi.org/10.1016/j.chom.2018.08.001] [PMID: 30146391]
[7]
Bussi, C.; Gutierrez, M.G. Mycobacterium tuberculosis infection of host cells in space and time. FEMS Microbiol. Rev., 2019, 43(4), 341-361.
[http://dx.doi.org/10.1093/femsre/fuz006] [PMID: 30916769]
[8]
Shariq, M.; Quadir, N.; Sharma, N.; Singh, J.; Sheikh, J.A.; Khubaib, M.; Hasnain, S.E.; Ehtesham, N.Z. Mycobacterium tuberculosis RipA dampens TLR4-Mediated host protective response using a multi-pronged approach involving autophagy, apoptosis, metabolic repurposing, and immune modulation. Front. Immunol., 2021, 12, 636644.
[http://dx.doi.org/10.3389/fimmu.2021.636644] [PMID: 33746976]
[9]
Bomfim, C.C.B.; Fisher, L.; Amaral, E.P.; Mittereder, L.; McCann, K.; Correa, A.A.S.; Namasivayam, S.; Swamydas, M.; Moayeri, M.; Weiss, J.M.; Chari, R.; McVicar, D.W.; Costa, D.L.; D’Império Lima, M.R.; Sher, A. Mycobacterium tuberculosis induces Irg1 in murine macrophages by a pathway involving both TLR-2 and STING/IFNAR signaling and requiring bacterial phagocytosis. Front. Cell. Infect. Microbiol., 2022, 12, 862582.
[http://dx.doi.org/10.3389/fcimb.2022.862582] [PMID: 35586249]
[10]
Arbués, A.; Brees, D.; Chibout, S.D.; Fox, T.; Kammüller, M.; Portevin, D. TNF-α antagonists differentially induce TGF-β1-dependent resuscitation of dormant-like Mycobacterium tuberculosis. PLoS Pathog., 2020, 16(2), e1008312.
[http://dx.doi.org/10.1371/journal.ppat.1008312] [PMID: 32069329]
[11]
Chen, Y.C.; Lee, C.P.; Hsiao, C.C.; Hsu, P.Y.; Wang, T.Y.; Wu, C.C.; Chao, T.Y.; Leung, S.Y.; Chang, Y.P.; Lin, M.C. MicroRNA-23a-3p down-regulation in active pulmonary tuberculosis patients with high bacterial burden inhibits mononuclear cell function and phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 signaling via targeting IRF1/SP1. Int. J. Mol. Sci., 2020, 21(22), 8587.
[http://dx.doi.org/10.3390/ijms21228587] [PMID: 33202583]
[12]
Adankwah, E.; Nausch, N.; Minadzi, D.; Abass, M.K.; Franken, K.L.M.C.; Ottenhoff, T.H.M.; Mayatepek, E.; Phillips, R.O.; Jacobsen, M. Interleukin-6 and Mycobacterium tuberculosis dormancy antigens improve diagnosis of tuberculosis. J. Infect., 2021, 82(2), 245-252.
[http://dx.doi.org/10.1016/j.jinf.2020.11.032] [PMID: 33278400]
[13]
Saghazadeh, A.; Rezaei, N. Central inflammatory cytokines in tuberculous meningitis: A systematic review and meta-analysis. J. Interferon Cytokine Res., 2022, 42(3), 95-107.
[http://dx.doi.org/10.1089/jir.2021.0176] [PMID: 35298290]
[14]
Petruccioli, E.; Petrone, L.; Chiacchio, T.; Farroni, C.; Cuzzi, G.; Navarra, A.; Vanini, V.; Massafra, U.; Lo Pizzo, M.; Guggino, G.; Caccamo, N.; Cantini, F.; Palmieri, F.; Goletti, D. Mycobacterium tuberculosis immune response in patients with immune-mediated inflammatory disease. Front. Immunol., 2021, 12, 716857.
[http://dx.doi.org/10.3389/fimmu.2021.716857] [PMID: 34447382]
[15]
Mehta, M.; Singh, A. Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species. Free Radic. Biol. Med., 2019, 131, 50-58.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.032] [PMID: 30500421]
[16]
Xu, L.; Cui, G.; Jia, H.; Zhu, Y.; Ding, Y.; Chen, J.; Lu, C.; Ye, P.; Gao, H.; Li, L.; Ma, W.; Lyu, J.; Diao, H. Decreased IL-17 during treatment of sputum smear-positive pulmonary tuberculosis due to increased regulatory T cells and IL-10. J. Transl. Med., 2016, 14(1), 179.
[http://dx.doi.org/10.1186/s12967-016-0909-6] [PMID: 27311307]
[17]
Patel, B.V.; Wilson, M.R.; O’Dea, K.P.; Takata, M. TNF-induced death signaling triggers alveolar epithelial dysfunction in acute lung injury. J. Immunol., 2013, 190(8), 4274-4282.
[http://dx.doi.org/10.4049/jimmunol.1202437] [PMID: 23487422]
[18]
Esquivel, B.; Sanchez, A.A. Rearranged icetexane diterpenoids from the roots of Salvia thymoides (Labiatae). Nat. Prod. Res., 2005, 19(4), 413-417.
[http://dx.doi.org/10.1080/14786410512331328731] [PMID: 15938149]
[19]
Esquivel, B.; Sánchez, A.A.; Vergara, F.; Matus, W.; Hernandez-Ortega, S.; Ramírez-Apan, M.T. Abietane diterpenoids from the roots of some Mexican Salvia species (Labiatae): Chemical diversity, phytogeographical significance, and cytotoxic activity. Chem. Biodivers., 2005, 2(6), 738-747.
[http://dx.doi.org/10.1002/cbdv.200590051] [PMID: 17192017]
[20]
Esquivel, B.; Bustos-Brito, C.; Sánchez-Castellanos, M.; Nieto-Camacho, A.; Ramírez-Apan, T.; Joseph-Nathan, P.; Quijano, L. Structure, absolute configuration, and antiproliferative activity of abietane and icetexane diterpenoids from salvia ballotiflora. Molecules, 2017, 22(10), 1690.
[http://dx.doi.org/10.3390/molecules22101690] [PMID: 29057832]
[21]
Bustos-Brito, C.; Joseph-Nathan, P.; Burgueño-Tapia, E.; Martínez-Otero, D.; Nieto-Camacho, A.; Calzada, F.; Yépez-Mulia, L.; Esquivel, B.; Quijano, L. Structure and absolute configuration of abietane diterpenoids from Salvia clinopodioides: Antioxidant, antiprotozoal, and antipropulsive activities. J. Nat. Prod., 2019, 82(5), 1207-1216.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00952] [PMID: 31063376]
[22]
Leonard, B.; Coronel, J.; Siedner, M.; Grandjean, L.; Caviedes, L.; Navarro, P.; Gilman, R.H.; Moore, D.A.J. Inter- and intra-assay reproducibility of microplate Alamar blue assay results for isoniazid, rifampicin, ethambutol, streptomycin, ciprofloxacin, and capreomycin drug susceptibility testing of Mycobacterium tuberculosis. J. Clin. Microbiol., 2008, 46(10), 3526-3529.
[http://dx.doi.org/10.1128/JCM.02083-07] [PMID: 18701659]
[23]
Abbas, A.K.; Lichtman, A.H.; Pillai, S. Cellular and Molecular Immunology, 9th ed; Elsevier Science: Boston, MA, 2018.
[24]
Pleuger, C.; Silva, E.J.R.; Pilatz, A.; Bhushan, S.; Meinhardt, A. Differential immune response to infection and acute inflammation along the epididymis. Front. Immunol., 2020, 11, 599594.
[http://dx.doi.org/10.3389/fimmu.2020.599594] [PMID: 33329594]
[25]
Kumar, V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Front. Immunol., 2020, 11, 1722.
[http://dx.doi.org/10.3389/fimmu.2020.01722] [PMID: 32849610]
[26]
Mortaz, E.; Adcock, I.M.; Tabarsi, P.; Masjedi, M.R.; Mansouri, D.; Velayati, A.A.; Casanova, J.L.; Barnes, P.J. Interaction of pattern recognition receptors with Mycobacterium tuberculosis. J. Clin. Immunol., 2015, 35(1), 1-10.
[http://dx.doi.org/10.1007/s10875-014-0103-7] [PMID: 25312698]
[27]
Landes, M.B.; Rajaram, M.V.S.; Nguyen, H.; Schlesinger, L.S. Role for NOD2 in Mycobacterium tuberculosis -induced iNOS expression and NO production in human macrophages. J. Leukoc. Biol., 2015, 97(6), 1111-1119.
[http://dx.doi.org/10.1189/jlb.3A1114-557R] [PMID: 25801769]
[28]
Welin, A.; Eklund, D.; Stendahl, O.; Lerm, M. Human macrophages infected with a high burden of ESAT-6-expressing M. tuberculosis undergo caspase-1- and cathepsin B-independent necrosis. PLoS One, 2011, 6(5), e20302.
[http://dx.doi.org/10.1371/journal.pone.0020302] [PMID: 21637850]
[29]
Ravimohan, S.; Kornfeld, H.; Weissman, D.; Bisson, G.P. Tuberculosis and lung damage: From epidemiology to pathophysiology. Eur. Respir. Rev., 2018, 27(147), 170077.
[http://dx.doi.org/10.1183/16000617.0077-2017] [PMID: 29491034]
[30]
Naeem, M.A.; Ahmad, W.; Tyagi, R.; Akram, Q.; Younus, M.; Liu, X. Stealth strategies of Mycobacterium tuberculosis for immune evasion. Curr. Issues Mol. Biol., 2021, 41, 597-616.
[http://dx.doi.org/10.21775/cimb.041.597] [PMID: 33068079]
[31]
Mahamed, D.; Boulle, M.; Ganga, Y.; Mc Arthur, C.; Skroch, S.; Oom, L.; Catinas, O.; Pillay, K.; Naicker, M.; Rampersad, S.; Mathonsi, C.; Hunter, J.; Wong, E.B.; Suleman, M.; Sreejit, G.; Pym, A.S.; Lustig, G.; Sigal, A. Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells. eLife, 2017, 6, e22028.
[http://dx.doi.org/10.7554/eLife.22028] [PMID: 28130921]
[32]
Vir, P.; Gupta, D.; Agarwal, R.; Verma, I. Immunomodulation of alveolar epithelial cells by Mycobacterium tuberculosis phosphatidylinositol mannosides results in apoptosis. Acta Pathol. Microbiol. Scand. Suppl., 2014, 122(4), 268-282.
[http://dx.doi.org/10.1111/apm.12141] [PMID: 23919648]
[33]
Ndjoubi, K.O.; Sharma, R.; Hussein, A.A. The potential of natural diterpenes against tuberculosis: An updated review. Curr. Pharm. Des., 2020, 26(24), 2909-2932.
[http://dx.doi.org/10.2174/1381612826666200612163326] [PMID: 32532186]
[34]
de Carvalho, H.C.; Ieque, A.L.; Valverde, T.L.; Baldin, V.P.; Meneguello, J.E.; Campanerut-Sá, P.A.Z.; Vandresen, F.; Ghiraldi Lopes, L.D.; Passos Souza, M.R.; Santos, N.C.S.; Dias Siqueira, V.L.; Caleffi-Ferracioli, K.R.; Lima Scodro, R.B.; Cardoso, R.F. Activity of (-)-camphene derivatives against mycobacterium tuberculosis in acidic pH. Med. Chem., 2021, 17(5), 485-492.
[http://dx.doi.org/10.2174/1573406415666191106124016] [PMID: 31702530]
[35]
Zhu, C.Z.; Hu, B.Y.; Liu, J.W.; Cai, Y.; Chen, X.C.; Qin, D.P.; Cheng, Y.X.; Zhang, Z.D. Anti-mycobacterium tuberculosis terpenoids from Resina commiphora. Molecules, 2019, 24(8), 1475.
[http://dx.doi.org/10.3390/molecules24081475]
[36]
Nakamura de Vasconcelos, S.S.; Caleffi-Ferracioli, K.R.; Hegeto, L.A.; Baldin, V.P.; Nakamura, C.V.; Stefanello, T.F.; Freitas Gauze, G.; Yamazaki, D.A.S.; Scodro, R.B.L.; Siqueira, V.L.D.; Cardoso, R.F. Carvacrol activity & morphological changes in Mycobacterium tuberculosis. Future Microbiol., 2018, 13(8), 877-888.
[http://dx.doi.org/10.2217/fmb-2017-0232] [PMID: 29877104]
[37]
Sieniawska, E.; Sawicki, R.; Marchev, A.S.; Truszkiewicz, W.; Georgiev, M.I. Tanshinones from Salvia miltiorrhiza inhibit Mycobacterium tuberculosis via disruption of the cell envelope surface and oxidative stress. Food Chem. Toxicol., 2021, 156, 112405.
[http://dx.doi.org/10.1016/j.fct.2021.112405]
[38]
Zerin, T.; Lee, M.; Jang, W.S.; Nam, K.W.; Song, H. Ursolic acid reduces Mycobacterium tuberculosis-induced nitric oxide release in human alveolar A549 cells. Mol. Cells, 2015, 38(7), 610-615.
[http://dx.doi.org/10.14348/molcells.2015.2328] [PMID: 26084752]
[39]
He, W.; Sun, J.; Zhang, Q.; Li, Y.; Fu, Y.; Zheng, Y.; Jiang, X. Andrographolide exerts anti-inflammatory effects in Mycobacterium tuberculosis -infected macrophages by regulating the Notch1/Akt/NF-κB axis. J. Leukoc. Biol., 2020, 108(6), 1747-1764.
[http://dx.doi.org/10.1002/JLB.3MA1119-584RRR] [PMID: 32991757]
[40]
García-Davis, S.; Leal-López, K.; Molina-Torres, C.A.; Vera-Cabrera, L.; Díaz-Marrero, A.R.; Fernández, J.J.; Carranza-Rosales, P.; Viveros-Valdez, E. Antimycobacterial activity of laurinterol and aplysin from Laurencia johnstonii. Mar. Drugs, 2020, 18(6), 287.
[http://dx.doi.org/10.3390/md18060287] [PMID: 32486286]
[41]
de Oliveira, J.A.M.; Williams, D.E.; Bonnett, S.; Johnson, J.; Parish, T.; Andersen, R.J. Diterpenoids isolated from the Samoan marine sponge Chelonaplysilla sp. inhibit Mycobacterium tuberculosis growth. J. Antibiot., 2020, 73(8), 568-573.
[http://dx.doi.org/10.1038/s41429-020-0315-4] [PMID: 32404991]
[42]
Yu, Z.; Wei, Y.; Tian, X.; Yan, Q.; Yan, Q.; Huo, X.; Wang, C.; Sun, C.; Zhang, B.; Ma, X. Diterpenoids from the roots of Euphorbia ebracteolata and their anti-tuberculosis effects. Bioorg. Chem., 2018, 77, 471-477.
[http://dx.doi.org/10.1016/j.bioorg.2018.02.007] [PMID: 29453078]
[43]
González, Y.; Doens, D.; Santamaría, R.; Ramos, M.; Restrepo, C.M.; Barros de Arruda, L.; Lleonart, R.; Gutiérrez, M.; Fernández, P.L. A pseudopterane diterpene isolated from the octocoral Pseudopterogorgia acerosa inhibits the inflammatory response mediated by TLR-ligands and TNF-alpha in macrophages. PLoS One, 2013, 8(12), e84107.
[http://dx.doi.org/10.1371/journal.pone.0084107] [PMID: 24358331]
[44]
Chen, X.L.; Liu, F.; Xiao, X.R.; Yang, X.W.; Li, F. Anti-inflammatory abietanes diterpenoids isolated from Tripterygium hypoglaucum. Phytochemistry, 2018, 156, 167-175.
[http://dx.doi.org/10.1016/j.phytochem.2018.10.001] [PMID: 30312932]
[45]
Tran, Q.T.N.; Wong, W.S.F.; Chai, C.L.L. Labdane diterpenoids as potential anti-inflammatory agents. Pharmacol. Res., 2017, 124, 43-63.
[http://dx.doi.org/10.1016/j.phrs.2017.07.019] [PMID: 28751221]
[46]
Pecora, N.D.; Gehring, A.J.; Canaday, D.H.; Boom, W.H.; Harding, C.V. Mycobacterium tuberculosis LprA is a lipoprotein agonist of TLR2 that regulates innate immunity and APC function. J. Immunol., 2006, 177(1), 422-429.
[http://dx.doi.org/10.4049/jimmunol.177.1.422] [PMID: 16785538]
[47]
Noss, E.H.; Pai, R.K.; Sellati, T.J.; Radolf, J.D.; Belisle, J.; Golenbock, D.T.; Boom, W.H.; Harding, C.V. Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J. Immunol., 2001, 167(2), 910-918.
[http://dx.doi.org/10.4049/jimmunol.167.2.910] [PMID: 11441098]
[48]
Korb, V.; Chuturgoon, A.; Moodley, D. Mycobacterium tuberculosis: Manipulator of protective immunity. Int. J. Mol. Sci., 2016, 17(3), 131.
[http://dx.doi.org/10.3390/ijms17030131] [PMID: 26927066]
[49]
Saraav, I.; Singh, S.; Sharma, S. Outcome of Mycobacterium tuberculosis and Toll-like receptor interaction: Immune response or immune evasion? Immunol. Cell Biol., 2014, 92(9), 741-746.
[http://dx.doi.org/10.1038/icb.2014.52] [PMID: 24983458]
[50]
Kiran, D.; Podell, B.K.; Chambers, M.; Basaraba, R.J. Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: A review. Semin. Immunopathol., 2016, 38(2), 167-183.
[http://dx.doi.org/10.1007/s00281-015-0537-x] [PMID: 26510950]
[51]
Lachmandas, E.; Beigier-Bompadre, M.; Cheng, S.C.; Kumar, V.; van Laarhoven, A.; Wang, X.; Ammerdorffer, A.; Boutens, L.; de Jong, D.; Kanneganti, T.D.; Gresnigt, M.S.; Ottenhoff, T.H.M.; Joosten, L.A.B.; Stienstra, R.; Wijmenga, C.; Kaufmann, S.H.E.; van Crevel, R.; Netea, M.G. Rewiring cellular metabolism via the AKT/mTOR pathway contributes to host defence against Mycobacterium tuberculosis in human and murine cells. Eur. J. Immunol., 2016, 46(11), 2574-2586.
[http://dx.doi.org/10.1002/eji.201546259] [PMID: 27624090]
[52]
Tomioka, H.; Tatano, Y.; Shimizu, T.; Sano, C. Clinical and basic studies on therapeutic efficacy of herbal medicines against mycobacterial infections. Medicines, 2019, 6(2), 67.
[http://dx.doi.org/10.3390/medicines6020067] [PMID: 31248144]
[53]
Liu, T. Zhang, L.; Joo, D.; Sun, S.-C. NF-ΚB signaling in inflammation. Signal Transduct. Target. Ther., 2017, 2, 17023.
[http://dx.doi.org/10.1038/sigtrans.2017.23]
[54]
Dolcet, X.; Llobet, D.; Pallares, J.; Matias-Guiu, X. NF-kB in development and progression of human cancer. Virchows Arch., 2005, 446(5), 475-482.
[http://dx.doi.org/10.1007/s00428-005-1264-9] [PMID: 15856292]
[55]
Horiuchi, T.; Mitoma, H.; Harashima, S.; Tsukamoto, H.; Shimoda, T. Transmembrane TNF-: Structure, function and interaction with anti-TNF agents. Rheumatology, 2010, 49(7), 1215-1228.
[http://dx.doi.org/10.1093/rheumatology/keq031] [PMID: 20194223]
[56]
Ruiz, A.; Palacios, Y.; Garcia, I.; Chavez-Galan, L. Transmembrane TNF and its receptors TNFR1 and TNFR2 in mycobacterial infections. Int. J. Mol. Sci., 2021, 22(11), 5461.
[http://dx.doi.org/10.3390/ijms22115461] [PMID: 34067256]
[57]
Clark, D.A.; Coker, R. Molecules in focus Transforming growth factor-beta (TGF-β). Int. J. Biochem. Cell Biol., 1998, 30(3), 293-298.
[http://dx.doi.org/10.1016/S1357-2725(97)00128-3] [PMID: 9611771]
[58]
Robertson, I.B.; Horiguchi, M.; Zilberberg, L.; Dabovic, B.; Hadjiolova, K.; Rifkin, D.B. Latent TGF-β-binding proteins. Matrix Biol., 2015, 47, 44-53.
[http://dx.doi.org/10.1016/j.matbio.2015.05.005] [PMID: 25960419]
[59]
Barcellos-Hoff, M.H.; Dix, T.A. Redox-mediated activation of latent transforming growth factor-beta 1. Mol. Endocrinol., 1996, 10(9), 1077-1083.
[http://dx.doi.org/10.1210/mend.10.9.8885242] [PMID: 8885242]
[60]
Chang, M.; Nguyen, T.T. Strategy for treatment of infected diabetic foot ulcers. Acc. Chem. Res., 2021, 54(5), 1080-1093.
[http://dx.doi.org/10.1021/acs.accounts.0c00864] [PMID: 33596041]
[61]
Chang, C.H.; Pauklin, S. ROS and TGFβ From pancreatic tumour growth to metastasis. J. Exp. Clin. Cancer Res., 2021, 40(1), 152.
[http://dx.doi.org/10.1186/s13046-021-01960-4] [PMID: 33941245]
[62]
Shimura, T. Roles of fibroblasts in microenvironment formation associated with radiation-induced cancer. Adv. Exp. Med. Biol., 2021, 1329, 239-251.
[http://dx.doi.org/10.1007/978-3-030-73119-9_13] [PMID: 34664243]