Pulmonary fibrosis is a specific form of chronic progressive interstitial lung disease. Deposition of extracellular matrix, mainly collagen, is the pathogenic characteristic of pulmonary fibrosis. Many reports show that environmental pollutants, particularly asbestos, silica, mercury, cadmium, and benzo(a)pyrene, are contributed in the etiology of lung injury and a risk factor in the development of idiopathic pulmonary fibrosis (IPF) in humans. Based on its physicochemical properties, environmental pollutant-induced pulmonary fibrosis can be developed after a particular type or dose of exposure. To date, some studies have focused on variant pollutants that are induced. However, the molecular mechanism of various pollutants to cause lung injury, which leads to pulmonary fibrosis, remained unexplored. Hence, this narrative review articles describe its molecular mechanism in generating pulmonary fibrosis comprehensively. It is helpful to portray the IPF pathogenesis and its drug discovery and development. Collectively, this article also revealed animal models which can be useful for IPF drug development research.


Ahluwalia, N., Shea, B. S., Tager, A. M. (2014). New therapeutic targets in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 190(8), 867-78.

Aryal, S., Nathan, S. D. (2018). An update on emerging drugs for the treatment of idiopathic pulmonary fibrosis. Expert Opinion on Emerging Drugs, 23(2):159-172. https://doi.org/10.1080/14728214.2018.1471465

Ali, H. M. (2018). Mitigative role of garlic and vitamin E against cytotoxic, genotoxic, and apoptotic effects of lead acetate and mercury chloride on WI-38 cells. Pharmacological Reports, 70(4), 804–811. https://doi.org/10.1016/j.pharep.2018.02.009

Alzohairy, M. A., Khan, A. A., Alsahli, M. A., Almatroodi, S. A., & Rahmani, A. H. (2021). Protective Effects of Thymoquinone, an Active Compound of Nigella sativa, on Rats with Benzo ( a ) pyrene -Induced and Inflammation. Molecules, 26, 3218.

Assad, N., Sood, A., Campen, M. J., & Zychowski, K. E. (2018). Metal-Induced Pulmonary Fibrosis. Current Environmental Health Reports, 5, 486–498.

Azari, M. R., Mohammadian, Y., Peirovi, H., Omidi, M., Khodagholi, F., Pourahmad, J., Mehrabi, Y., & Rafieepour, A. (2019). Antagonistic effect of co-exposure to short-multiwalled carbon nanotubes and benzo[a]pyrene in human lung cells (A549). Toxicology and Industrial Health, 35(6), 445–456. https://doi.org/10.1177/0748233719854570

Bala, G.-P., Rajnoveanu, R.-M., Tudorache, E., Motisan, R., & Oancea, C. (2021). Air pollution exposure — the (in) visible risk factor for respiratory diseases. Environmental Science and Pollution Research, 28, 19615–19628.

Barnwal, P., Vafa, A., Afzal, S. M., Shahid, A., Hasan, S. K., Alpashree, & Sultana, S. (2018). Benzo(a)pyrene induces lung toxicity and inflammation in mice: prevention by carvacrol. Human and Experimental Toxicology, 37(7), 752–761. https://doi.org/10.1177/0960327117735572

Berngard, S. C., & Afshar, K. (2016). Idiopathic pulmonary fibrosis: Past, present, future-a review from Talmadge King's ATS 2016 presentation. Journal of Thoracic Disease, 8(7), S559–S561. https://doi.org/10.21037/jtd.2016.07.31

Bhagia, L. (2012). Non-occupational exposure to silica dust. Indian Journal of Occupational and Environmental Medicine, 16(3), 95–100. https://doi.org/10.4103/0019-5278.111744

Bo, C., Geng, X., Zhang, J., Sai, L., Zhang, Y., Yu, G., Zhang, Z., Liu, K., Du, Z., Peng, C., Jia, Q., & Shao, H. (2020). Comparative proteomic analysis of silica-induced pulmonary fibrosis in rats based on tandem mass tag (TMT) quantitation technology. PLoS ONE, 15(10 October), 1–15. https://doi.org/10.1371/journal.pone.0241310

Brown, T. P., & Rushton, L. (2005). Mortality in the UK industrial silica sand industry: 2. A retrospective cohort study. Occupational and Environmental Medicine, 62(7), 446–452. https://doi.org/10.1136/oem.2004.017731

Byczkowski, J. Z., & Kulkarni, A. P. (1990). Lipid peroxidation and benzo(a)pyrene derivative co-oxygenation by environmental pollutants. Bulletin of Environmental Contamination and Toxicology, 45(5), 633–640. https://doi.org/10.1007/BF01700979

Campopiano, A., Cannizzaro, A., Olori, A., Angelosanto, F., Rosaria, M., Sinopoli, F., Maria, B., Casalinuovo, F., & Iavicoli, S. (2020). Environmental contamination by naturally occurring asbestos (NOA): Analysis of sentinel animal lung tissue Antonella. Science of the Total Environment, 745, 140990. https://doi.org/10.1016/j.scitotenv.2020.140990

Carrell, C. J., Carrell, T. G., Carrell, H. L., Prout, K., & Glusker, J. P. (1997). Benzo[a]pyrene and its analogues: Structural studies of molecular strain. Carcinogenesis, 18(2), 415–422. https://doi.org/10.1093/carcin/18.2.415

Cedillo-Pozos, A., Ternovoy, S. K., & Roldan-Valadez, E. (2020). Imaging methods used in the assessment of environmental disease networks: a brief review for clinicians. Insights into Imaging, 11(1). https://doi.org/10.1186/s13244-019-0814-7

Chen, J. H., Chou, F. P., Lin, H. H., & Wang, C. J. (2005). Gaseous nitrogen oxide repressed benzo[a]pyrene-induced human lung fibroblast cell apoptosis via inhibiting JNK1 signals. Archives of Toxicology, 79(12), 694–704. https://doi.org/10.1007/s00204-005-0001-0

Cheresh, P., Kim, S. J., Huang, L. S., Watanabe, S., Joshi, N., Williams, K. J. N., Chi, M., Lu, Z., Harijith, A., Yeldandi, A., Lam, A. P., Gottardi, C., Misharin, A. V., Budinger, G. R. S., Natarajan, V., & Kamp, D. W. (2020). The sphingosine kinase 1 inhibitor, pf543, mitigates pulmonary fibrosis by reducing lung epithelial cell mtdna damage and recruitment of fibrogenic monocytes. International Journal of Molecular Sciences, 21(16), 1–17. https://doi.org/10.3390/ijms21165595

Croissant, J. G., Butler, K. S., Zink, J. I., & Brinker, C. J. (2020). Synthetic amorphous silica nanoparticles: toxicity, biomedical and environmental implications. Nature Reviews Materials, 5(12), 886–909. https://doi.org/10.1038/s41578-020-0230-0

Cui, Y., Zha, Y., Li, T., Bai, J., Tang, L., Deng, J., He, R., Dong, F., & Zhang, Q. (2019). Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile. Environmental Science and Pollution Research, 26(18), 18708–18718. https://doi.org/10.1007/s11356-019-04978-6

Cuypers, A., Plusquin, M., Remans, T., Jozefczak, M., Keunen, E., Gielen, H., Opdenakker, K., Nair, A. R., Munters, E., Artois, T. J., Nawrot, T., Vangronsveld, J., & Smeets, K. (2010). Cadmium stress: An oxidative challenge. BioMetals, 23(5), 927–940. https://doi.org/10.1007/s10534-010-9329-x

Daniel, L. N., Mao, Y., & Saffiotti, U. (1993). Oxidative DNA damage by crystalline silica. Free Radical Biology and Medicine, 14, 463–472.

Daniel, L. N., Mao, Y., Wang, T. C., Markey, C. J., Markey, S. P., Shi, X., & Saffiotti, U. (1995). DNA strand breakage, thymine glycol production, and hydroxyl radical generation induced by different samples of crystalline silica in vitro. Environmental Research, 71, 60–73.

Drakopanagiotakis, F., Wujak, L., Wygrecka, M., & Markart, P. (2018). Biomarkers in idiopathic pulmonary fibrosis. Matrix Biology, 6869, 404–421. https://doi.org/10.1016/j.matbio.2018.01.023

European Respiratory Society. (2013). Interstitial lung diseases. In G. J. Gibson, R. Loddenkemper, Y. Sibille, & B. Lundbäck (Eds.), The European Lung White Book (pp. 256–269). https://doi.org/10.1183/2312508X.10003015

Feng, F., Cheng, P., Zhang, H., Li, N., Qi, Y., Wang, H., Wang, Y., & Wang, W. (2019). The protective role of tanshinone IIA in silicosis rat model via TGF-β1/smad signaling suppression, NOX4 inhibition and Nrf2/ARE signaling activation. Drug Design, Development and Therapy, 13, 4275–4290. https://doi.org/10.2147/DDDT.S230572

Fiducia, T. A. M., Mendis, B. G., Li, K., Grovenor, C. R. M., Munshi, A. H., Barth, K., Sampath, W. S., Wright, L. D., Abbas, A., Bowers, J. W., & Walls, J. M. (2019). Understanding the role of selenium in defect passivation for highly efficient selenium-alloyed cadmium telluride solar cells. Nature Energy, 4(6), 504–511. https://doi.org/10.1038/s41560-019-0389-z

Funahashi, S., Okazaki, Y., Ito, D., Asakawa, A., Nagai, H., Tajima, M., & Toyokuni, S. (2015). Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. Journal of Clinical Biochemistry and Nutrition, 56(2), 111–117. https://doi.org/10.3164/jcbn.14-92

Glass, D.S., Grossfeld, D., Renna, H.A., Agarwala, P., Spiegler, P., Kasselman, L.J., DeLeon, J., Reis, A.B. (2020). Idiopathic pulmonary fibrosis: molecular mechanisms and potential treatment approaches. Respiratory Investigation, 58(2). https://doi.org/10.1016/j.resinv.2020.04.002

Ganguly, K., Levänen, B., Palmberg, L., Åkesson, A., & Lindén, A. (2018). Cadmium in tobacco smokers: A neglected link to lung disease?. European Respiratory Review, 27(147), 1–8. https://doi.org/10.1183/16000617.0122-2017

Gibbs, A. R., Attanoos, R., Popper, H. H., & Corrin, B. (2014). Pathology of Asbestosis — An Update of the Diagnostic Criteria. May. https://doi.org/10.1043/1543-2165-134.3.462

Guo, J., Yang, Z., Jia, Q., Bo, C., Shao, H., & Zhang, Z. (2019). Pirfenidone inhibits epithelial-mesenchymal transition and pulmonary fibrosis in the rat silicosis model. Toxicology Letters, 300(October 2018), 59–66. https://doi.org/10.1016/j.toxlet.2018.10.019

Hamoudah, S. Y. ., El Naggar, S. I., & H.H, H. (2002). Histopathological and Biochemical Evaluation of the Pulmonary Toxicity of Cadmium Chloride and thiocarbamate. The Egyptian Journal of Hospital Medicine, 7(1), 28–40. https://doi.org/10.21608/ejhm.2002.18818

Harari, S., Raghu, G., Caminati, A., Cruciani, M., Franchini, M., & Mannucci, P. (2020). Fibrotic interstitial lung diseases and air pollution: A systematic literature review. European Respiratory Review, 29(157), 1–8. https://doi.org/10.1183/16000617.0093-2020

He, C., Larson-Casey, J. L., Davis, D., Hanumanthu, V. S., Longhini, A. L. F., Thannickal, V. J., Gu, L., & Brent Carter, A. (2019). NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis. JCI Insight, 4(16). https://doi.org/10.1172/jci.insight.126551

Hu, X., Fernandes, J., Jones, D. P., & Go, Y. M. (2017). Cadmium stimulates myofibroblast differentiation and mouse lung fibrosis. Toxicology, 383(November 2016), 50–56. https://doi.org/10.1016/j.tox.2017.03.018

Huang, Z., Wang, S., Liu, Y., Fan, L., Zeng, Y., Han, H., Zhang, H., Yu, X., Zhang, Y., Huang, D., Wu, Y., Jiang, W., Zhu, P., Zhu, X., & Yi, X. (2020). GPRC5A reduction contributes to pollutant benzo[a]pyrene injury via aggravating murine fibrosis, leading to poor prognosis of IIP patients. Science of the Total Environment, 739(389), 139923. https://doi.org/10.1016/j.scitotenv.2020.139923

Hung, L. Y., Sen, D., Oniskey, T. K., Katzen, J., Cohen, N. A., Vaughan, A. E., Nieves, W., Urisman, A., Beers, M. F., Krummel, M. F., & Herbert, D. B. R. (2018). Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism. Mucosal Immunology, 12(1), 64-76. https://doi.org/10.1038/s41385-018-0096-2

Hýžďalová, M., Procházková, J., Strapáčová, S., Svržková, L., Vacek, O., Fedr, R., Andrysík, Z., Hrubá, E., Líbalová, H., Kléma, J., Topinka, J., Mašek, J., Souček, K., Vondráček, J., & Machala, M. (2021). A prolonged exposure of human lung carcinoma epithelial cells to benzo[a]pyrene induces p21-dependent epithelial-to-mesenchymal transition (EMT)-like phenotype. Chemosphere, 263. https://doi.org/10.1016/j.chemosphere.2020.128126

Jafari, S., Derakhshankhah, H., Alaei, L., Fattahi, A., Varnamkhasti, B. S., & Saboury, A. A. (2019). Mesoporous silica nanoparticles for therapeutic/diagnostic applications. Biomedicine and Pharmacotherapy, 109(August 2018), 1100–1111. https://doi.org/10.1016/j.biopha.2018.10.167

Janssens, W., & van Bleyenbergh, P. (2020). Lung function in asthma, chronic obstructive pulmonary disease and lung fibrosis. In R. L. Maynard, S. J. Pearce, B. Nemery, P. D. Wagner, & B. G. Cooper (Eds.), Cotes' Lung Function (7th ed., pp. 681–696). Wiley Blackwell.

Kamp, D. W., Liu, G., Cheresh, P., Kim, S. J., Mueller, A., Lam, A. P., Trejo, H., Williams, D., Tulasiram, S., Baker, M., Ridge, K., Chandel, N. S., & Beri, R. (2013). Asbestos-induced alveolar epithelial cell apoptosis: The role of endoplasmic reticulum stress response. American Journal of Respiratory Cell and Molecular Biology, 49(6), 892–901. https://doi.org/10.1165/rcmb.2013-0053OC

Kim, J. Y., An, M. J., Shin, G. S., Lee, H. M., Kim, M. J., Kim, C. H., & Kim, J. W. (2021). Mercury chloride but not lead acetate causes apoptotic cell death in human lung fibroblast mrc5 cells via regulation of cell cycle progression. International Journal of Molecular Sciences, 22(5), 1–14. https://doi.org/10.3390/ijms22052494

Kimura, K., Nakano, Y., Sugizaki, T., Shimoda, M., Kobayashi, N., Kawahara, M., & Tanaka, K. I. (2019). Protective effect of polaprezinc on cadmium-induced injury of lung epithelium. Metallomics, 11(7), 1310–1320. https://doi.org/10.1039/c9mt00060g

Kleaveland, K. R., Velikoff, M., Yang, J., Agarwal, M., Rippe, R. A., Moore, B. B., & Kim, K. K. (2014). Fibrocytes Are Not an Essential Source of Type I Collagen during Lung Fibrosis. The Journal of Immunology, 193(10), 5229–5239. https://doi.org/10.4049/jimmunol.1400753

Kumar, K. M. K., Kumar, M. N., Patil, R. H., Nagesh, R., Hegde, S. M., Kavya, K., Babu, R. L., Ramesh, G. T., & Sharma, S. C. (2016). Cadmium induces oxidative stress and apoptosis in lung epithelial cells. In Toxicology Mechanisms and Methods (Vol. 26, Issue 9). https://doi.org/10.1080/15376516.2016.1223240

Kundu, S., Sengupta, S., Chatterjee, S., Mitra, S., & Bhattacharyya, A. (2009). Cadmium induces lung inflammation independent of lung cell proliferation: A molecular approach. Journal of Inflammation, 6, 1–15. https://doi.org/10.1186/1476-9255-6-19

Lazarus, A. A., & Philip, A. (2011). Asbestosis. Disease-a-Month, 57(1), 14–26. https://doi.org/10.1016/j.disamonth.2010.11.004

Li, J., Yao, W., Hou, J. Y., Lin, Z., Bao, L., Chen, H. T., Wang, D., Yue, Z. Z., Li, Y. P., Zhang, M., & Hao, C. F. (2017). Crystalline silica promotes rat fibrocyte differentiation in vitro, and fibrocytes participate in silicosis in vivo. Biomedical and Environmental Sciences, 30(9), 649–660. https://doi.org/10.3967/bes2017.086

Lilis, R., Miller, A., & Lerman, Y. (1985). Acute mercury poisoning with severe chronic pulmonary Manifestations. CHEST, 88(2), 306–309. https://doi.org/10.1378/chest.88.2.306

Lim, H. E., Shim, J. J., Lee, S. Y., Lee, S. H., Kang, S. Y., Jo, J. Y., In, K. H., Kim, H. G., Yoo, S. H., & Kang, K. H. (1998). Mercury inhalation poisoning and acute lung injury. The Korean Journal of Internal Medicine, 13(2), 127–130.

Lin, Z., Liu, T., Kamp, D. W., Wang, Y., He, H., Zhou, X., Li, D., Yang, L., Zhao, B., & Liu, G. (2014). AKT/mTOR and c-Jun N-terminal kinase signaling pathways are required for chrysotile asbestos-induced autophagy. Free Radical Biology and Medicine, 72, 296–307. https://doi.org/10.1016/j.freeradbiomed.2014.04.004

Liu, B., Yu, H., Baiyun, R., Lu, J., Li, S., Bing, Q., Zhang, X., & Zhang, Z. (2018). Protective effects of dietary luteolin against mercuric chloride-induced lung injury in mice: Involvement of AKT/Nrf2 and NF-κB pathways. Food and Chemical Toxicology, 113(July 2017), 296–302. https://doi.org/10.1016/j.fct.2018.02.003

Liu, K., Wang, S., Wu, Q., Wang, L., Ma, Q., Zhang, L., Li, G., Tian, H., Duan, L., & Hao, J. (2018). A highly resolved mercury emission inventory of Chinese coal-fired power plants. Environmental Science and Technology, 52(4), 2400–2408. https://doi.org/10.1021/acs.est.7b06209

Liu, Y., Li, Y., Xu, Q., Yao, W., Wu, Q., Yuan, J., Yan, W., Xu, T., Ji, X., & Ni, C. (2018). Long non-coding RNA-ATB promotes EMT during silica-induced pulmonary fibrosis by competitively binding miR-200c. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1864(2), 420–431. https://doi.org/10.1016/j.bbadis.2017.11.003

Majewski, S., & Piotrowski, W. J. (2020). Air pollution—an overlooked risk factor for idiopathic pulmonary fibrosis. Journal of Clinical Medicine, 10(1), 77. https://doi.org/10.3390/jcm10010077

Meyer, K. C., Raghu, G., Baughman, R. P., Brown, K. K., Costabel, U., Du Bois, R. M., Drent, M., Haslam, P. L., Kim, D. S., Nagai, S., Rottoli, P., Saltini, C., Selman, M., Strange, C., & Wood, B. (2012). An official American Thoracic Society clinical practice guideline: The clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. American Journal of Respiratory and Critical Care Medicine, 185(9), 1004–1014. https://doi.org/10.1164/rccm.201202-0320ST

Murray, L. A., Chen, Q., Kramer, M. S., Hesson, D. P., Argentieri, R. L., Peng, X., Gulati, M., Homer, R. J., Russell, T., Van Rooijen, N., Elias, J. A., Hogaboam, C. M., & Herzog, E. L. (2011). TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. International Journal of Biochemistry and Cell Biology, 43(1), 154–162. https://doi.org/10.1016/j.biocel.2010.10.013

Naidoo, S. V. K., Bester, M. J., Arbi, S., Venter, C., Dhanraj, P., & Oberholzer, H. M. (2019). Oral exposure to cadmium and mercury alone and in combination causes damage to the lung tissue of Sprague-Dawley rats. Environmental Toxicology and Pharmacology, 69(March), 86–94. https://doi.org/10.1016/j.etap.2019.03.021

Nishimura, Y., Maeda, M., Kumagai-Takei, N., Lee, S., Matsuzaki, H., Wada, Y., Nishiike-Wada, T., Iguchi, H., & Otsuki, T. (2013). Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases. Environmental Health and Preventive Medicine, 18(3), 198–204. https://doi.org/10.1007/s12199-013-0333-y

O'Connor, D., Hou, D., Ok, Y. S., Mulder, J., Duan, L., Wu, Q., Wang, S., Tack, F. M. G., & Rinklebe, J. (2019). Mercury speciation, transformation, and transportation in soils, atmospheric flux, and implications for risk management: A critical review. Environment International, 126(November 2018), 747–761. https://doi.org/10.1016/j.envint.2019.03.019

Pan, Z., Guo, Y., Xiang, H., Hui, Y., Ju, H., Xu, S., & Li, L. (2020). Effects of Lead, Mercury, and Cadmium Co-exposure on Children's Pulmonary Function. Biological Trace Element Research, 194(1), 115–120. https://doi.org/10.1007/s12011-019-01772-w

Park, Y., Ahn, C., & Kim, T. H. (2021). Occupational and environmental risk factors of idiopathic pulmonary fibrosis: a systematic review and meta-analyses. Scientific Reports, 11(1), 1–10. https://doi.org/10.1038/s41598-021-81591-z

Pateda, S. M., Sakakibara, M., & Sera, K. (2018). Lung function assessment as an early biomonitor of mercury-induced health disorders in artisanal and small-scale gold mining areas in Indonesia. International Journal of Environmental Research and Public Health, 15(11), 14–23. https://doi.org/10.3390/ijerph15112480

Piersma, B., Bank, R. A., & Boersema, M. (2015). Signaling in Fibrosis: TGF-β, WNT, and YAP/TAZ Converge. Frontiers in Medicine, 2(September), 1–14. https://doi.org/10.3389/fmed.2015.00059

Pleasants, R., Tighe RM. (2019). Management of idiopathic pulmonary fibrosis. Annals of Pharmacotherapy. 53(12): 1238-48. https://doi.org/10.1177%2F1060028019862497

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., … Schünemann, H. J. (2011). An Official ATS/ERS/JRS/ALAT Statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. American Journal of Respiratory and Critical Care Medicine, 183(6), 788–824. https://doi.org/10.1164/rccm.2009-040GL

Raghu, G., Remy-Jardin, M., Myers, J. L., Richeldi, L., Ryerson, C. J., Lederer, D. J., Behr, J., Cottin, V., Danoff, S. K., Morell, F., Flaherty, K. R., Wells, A., Martinez, F. J., Azuma, A., Bice, T. J., Bouros, D., Brown, K. K., Collard, H. R., Duggal, A., … Wilson, K. C. (2018). Diagnosis of idiopathic pulmonary fibrosis An Official ATS/ERS/JRS/ALAT Clinical practice guideline. American Journal of Respiratory and Critical Care Medicine, 198(5), e44–e68. https://doi.org/10.1164/rccm.201807-1255ST

Raghu G, Luca R. (2017). Current approaches to the management of idiopathic pulmonary fibrosis. Respiratory Medicine, 129:24-30. http://dx.doi.org/10.1016/j.rmed.2017.05.017

Rahaman, S. O., Tschumperlin, D. J., Mitchell, A., Rahaman, S. O., Grove, L. M., Paruchuri, S., Southern, B. D., Abraham, S., Niese, K. A., Scheraga, R. G., Ghosh, S., Thodeti, C. K., Zhang, D. X., Moran, M. M., Schilling, W. P., Tschumperlin, D. J., & Olman, M. A. (2014). TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice. Journal of Clinical Investigation, 124(12), 5225–5238. https://doi.org/10.1172/JCI75331.that

Reizer, E., Csizmadia, I. G., Palotás, Á. B., Viskolcz, B., & Fiser, B. (2019). Formation mechanism of benzo(a)pyrene: One of the most carcinogenic polycyclic aromatic hydrocarbons (PAH). Molecules, 24(6). https://doi.org/10.3390/molecules24061040

Sai, L., Yu, G., Bo, C., Zhang, Y., Du, Z., Li, C., Zhang, Z., Jia, Q., Shao, H., & Peng, C. (2019). Profiling long non-coding RNA changes in silica-induced pulmonary fibrosis in rat. Toxicology Letters, 310(March), 7–13. https://doi.org/10.1016/j.toxlet.2019.04.003

Sakai, N., & Tager, A. M. (2013). Fibrosis of two: Epithelial cell-fibroblast interactions in pulmonary fibrosis. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1832(7), 911–921. https://doi.org/10.1016/j.bbadis.2013.03.001

Şener, G., Sehirli, Ö., Tozan, A., Velioǧlu-Övunç, A., Gedik, N., & Omurtag, G. Z. (2007). Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats. Food and Chemical Toxicology, 45(4), 543–550. https://doi.org/10.1016/j.fct.2006.07.024

Shi, Y., Zeng, Z., Yu, J., Tang, B., Tang, R., & Xiao, R. (2020). The aryl hydrocarbon receptor: An environmental effector in the pathogenesis of fibrosis. Pharmacological Research, 160(August), 105180. https://doi.org/10.1016/j.phrs.2020.105180

Song, J. W., Jeong, Y. J., Kim, K. I., Choi, S. J., Lee, H. K., Lee, K. N., & Manzano, A. C. (2013). Environmental lung diseases: Clinical and imaging findings. Clinical Radiology, 68(3), 310–316. https://doi.org/10.1016/j.crad.2012.07.012

Stufano, A., Scardapane, A., Pia, M., Barbaro, F., Corradi, M., & Lovreglio, P. (2020). Clinical and radiological criteria for the differential diagnosis between asbestosis and idiopathic pulmonary fibrosis : Application in two cases. Med Lav, 112(2), 115–122. https://doi.org/10.23749/mdl.v112i2.10473

Suzuki, T., Hidaka, T., Kumagai, Y., & Yamamoto, M. (2020). Environmental pollutants and the immune response. Nature Immunology, 21(12), 1486–1495. https://doi.org/10.1038/s41590-020-0802-6

Velagacherla, V., Mehta, C.H., Nayak, Y., Nayak, U.Y. (2022). Molecular pathways and role of epigenetics in the idiopathic pulmonary fibrosis. Life Sciences, 291. https://doi.org/10.1016/j.lfs.2021.120283.

Vetrano, K. M., Morris, J. B., & Hubbard, A. K. (1992). Silica-induced pulmonary inflammation and fibrosis in mice is altered by acute exposure to nitrogen dioxide. Journal of Toxicology and Environmental Health, 37(3), 425–442. https://doi.org/10.1080/15287399209531681

Walters, G. I. (2020). Occupational exposures and idiopathic pulmonary fibrosis. Current Opinion in Allergy & Clinical Immunology, 20(2), 103–111. https://doi.org/10.1097/aci.0000000000000610

Wang, C., Wei, Z., Han, Z., Wang, J., Zhang, X., Wang, Y., Liu, Q., & Yang, Z. (2019). Neutrophil extracellular traps promote cadmium chloride-induced lung injury in mice. Environmental Pollution, 254, 113021. https://doi.org/10.1016/j.envpol.2019.113021

Wick, G., Grundtman, C., Mayerl, C., Wimpissinger, T.-F., Feichtinger, J., Zelger, B., Sgonc, R., & Wolfram, D. (2013). The Immunology of Fibrosis. In Annual Review of Immunology (Vol. 31, Issue 1). https://doi.org/10.1146/annurev-immunol-032712-095937

Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S, Kolb M. (2015). Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. European Respiratory Journal, 45:1434-45. http://doi.org/10.1183/09031936.00174914

Wynn, T. A., & Vannella, K. M. (2016). Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity, 44(3), 450–462. https://doi.org/10.1016/j.immuni.2016.02.015

Yamano, Y., Kagawa, J., Hanaoka, T., Takahashi, T., Kasai, H., Tsugane, S., & Watanabe, S. (1995). Oxidative DNA damage induced by silica in vivo. Environmental Research, 69, 102–107.

Yanagihara T, Sato S, Upagupta C, Kolb M. (2019). What have we learned from basic science studies on idiopathic pulmonary fibrosis?. European Respiratory Review, 28. https://doi.org/10.1183/16000617.0029-2019

Yanamala, N., Kisin, E. R., Gutkin, D. W., Shurin, M. R., Harper, M., & Shvedova, A. A. (2018). Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles. Journal of Toxicology and Environmental Health - Part A: Current Issues, 81(4), 60–79. https://doi.org/10.1080/15287394.2017.1408201

Ye, G., Gao, H., Zhang, X., Liu, X., Chen, J., Liao, X., Zhang, H., & Huang, Q. (2021). Aryl hydrocarbon receptor mediates benzo[a]pyrene-induced metabolic reprogramming in human lung epithelial BEAS-2B cells. Science of the Total Environment, 756, 144130. https://doi.org/10.1016/j.scitotenv.2020.144130

Zhang, Z., Shen, H. M., Zhang, Q. F., & Ong, C. N. (2000). Involvement of oxidative stress in crystalline silica-induced cytotoxicity and genotoxicity in rat alveolar macrophages. Environmental Research, 82(3), 245–252. https://doi.org/10.1006/enrs.1999.4025



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.