{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:57:23Z","timestamp":1772931443124,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES025191"],"award-info":[{"award-number":["ES025191"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["CHHE P30 ES025128"],"award-info":[{"award-number":["CHHE P30 ES025128"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Poorly soluble environmental antigens, including carbon pollutants, are thought to play a role in the incidence of human sarcoidosis, a chronic inflammatory granulomatous disease of unknown causation. Currently, engineered carbon products such as multiwall carbon nanotubes (MWCNT) are manufactured commercially and have been shown to elicit acute and chronic inflammatory responses in experimental animals, including the production of granulomas or fibrosis. Several years ago, we hypothesized that constructing an experimental model of chronic granulomatosis resembling that associated with sarcoidosis might be achieved by oropharyngeal instillation of MWCNT into mice. This review summarizes the results of our efforts to define mechanisms of granuloma formation and identify potential therapeutic targets for sarcoidosis. Evidence is presented linking findings from the murine MWCNT granuloma model to sarcoidosis pathophysiology. As our goal was to determine what pulmonary inflammatory pathways might be involved, we utilized mice of knock-out (KO) backgrounds which corresponded to deficiencies noted in sarcoidosis patients. A primary example of this approach was to study mice with a myeloid-specific knock-out of the lipid-regulated transcription factor, peroxisome proliferator-activated receptor gamma (PPAR\u03b3) which is strikingly depressed in sarcoidosis. Among the major findings associated with PPAR\u03b3 KO mice compared to wild-type were: (1) exacerbation of granulomatous and fibrotic histopathology in response to MWCNT; (2) elevation of inflammatory mediators; and (3) pulmonary retention of a potentially antigenic ESAT-6 peptide co-instilled with MWCNT. In line with these data, we also observed that activation of PPAR\u03b3 in wild-type mice by the PPAR\u03b3-specific ligand, rosiglitazone, significantly reduced both pulmonary granuloma and inflammatory mediator production. Similarly, recognition of a deficiency of ATP-binding cassette (ABC) lipid transporter ABCG1 in sarcoidosis led us to study MWCNT instillation in myeloid-specific ABCG1 KO mice. As anticipated, ABCG1 deficiency was associated with larger granulomas and increased levels of inflammatory mediators. Finally, a transcriptional survey of alveolar macrophages from MWCNT-instilled wild-type mice and human sarcoidosis patients revealed several common themes. One of the most prominent mediators identified in both human and mouse transcriptomic analyses was MMP12. Studies with MMP12 KO mice revealed similar acute reactions to those in wild-type but at chronic time points where wild-type maintained granulomatous disease, resolution occurred with MMP12 KO mice suggesting MMP12 is necessary for granuloma progression. In conclusion, these studies suggest that the MWCNT granuloma model has relevance to human sarcoidosis study, particularly with respect to immune-specific pathways.<\/jats:p>","DOI":"10.3390\/ijms22073705","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T04:13:51Z","timestamp":1617336831000},"page":"3705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Studies in a Murine Granuloma Model of Instilled Carbon Nanotubes: Relevance to Sarcoidosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Barbara P.","family":"Barna","sequence":"first","affiliation":[{"name":"Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anagha","family":"Malur","sequence":"additional","affiliation":[{"name":"Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Jane","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/2040622318790197","article-title":"Epidemiology of sarcoidosis: Current findings and future directions","volume":"9","author":"Arkema","year":"2018","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1164\/rccm.202002-0251ST","article-title":"Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline","volume":"201","author":"Crouser","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.3389\/fimmu.2020.01340","article-title":"Environmental Risk Factors for Sarcoidosis","volume":"11","author":"Judson","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"l5553","DOI":"10.1136\/bmj.l5553","article-title":"New advances in the management of pulmonary sarcoidosis","volume":"367","author":"Culver","year":"2019","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1164\/rccm.200402-249OC","article-title":"A case control etiologic study of sarcoidosis: Environmental and occupational risk factors","volume":"170","author":"Newman","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1378\/chest.116.5.1183","article-title":"The incidence, prevalence, and severity of sarcoidosis in New York City firefighters","volume":"116","author":"Prezant","year":"1999","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ajim.20924","article-title":"\u201cSarcoid like\u201d granulomatous pulmonary disease in World Trade Center disaster responders","volume":"54","author":"Crowley","year":"2011","journal-title":"Am. J. Ind. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1378\/chest.06-2114","article-title":"World Trade Center \u201cSarcoid-Like\u201d Granulomatous Pulmonary Disease in New York City Fire Department Rescue Workers","volume":"131","author":"Izbicki","year":"2007","journal-title":"Chest"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sunil, V.R., Radbel, J., Hussain, S., Vayas, K.N., Cervelli, J., Deen, M., Kipen, H., Udasin, I., Laumbach, R., and Sunderram, J. (2019). Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers. Int J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16050815"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/wnan.1317","article-title":"Carbon nanotubes: Potential medical applications and safety concerns","volume":"7","author":"Amenta","year":"2015","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"578290","DOI":"10.1155\/2013\/578290","article-title":"Carbon nanotubes: Applications in pharmacy and medicine","volume":"2013","author":"He","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1165\/rcmb.2010-0401OC","article-title":"Novel Murine Model of Chronic Granulomatous Lung Inflammation Elicited by Carbon Nanotubes","volume":"45","author":"Huizar","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1080\/01902140490476382","article-title":"Direct visual instillation as a method for efficient delivery of fluid into the distal airspaces of anesthetized mice","volume":"30","author":"Su","year":"2004","journal-title":"Exp. Lung Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/tox.20270","article-title":"Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intrtracheal instillation and inhalation","volume":"22","author":"Li","year":"2007","journal-title":"Environ. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/toxsci\/kfj123","article-title":"Comparative pulmonary toxicological assessment of oil combustion particles following inhalation or instillation exposure","volume":"91","author":"Costa","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/toxsci\/55.1.24","article-title":"Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: Uses and limitations","volume":"55","author":"Driscoll","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L617","DOI":"10.1152\/ajplung.00289.2017","article-title":"Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis","volume":"314","author":"Mohan","year":"2018","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1164\/ajrccm.164.12.2104139","article-title":"Abnormal pulmonary granuloma formation in osteopontin-deficient mice","volume":"164","author":"Hayden","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.bbamcr.2017.05.010","article-title":"Matrix metalloproteinases as regulators of inflammatory processes","volume":"1864","author":"Fingleton","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.imbio.2007.09.012","article-title":"The molecular basis of macrophage fusion","volume":"212","author":"Helming","year":"2007","journal-title":"Immunobiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases","volume":"2","author":"Tyagi","year":"2011","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.it.2007.09.003","article-title":"Anti-inflammatory actions of PPAR ligands: New insights on cellular and molecular mechanisms","volume":"28","author":"Straus","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23812","DOI":"10.1155\/2007\/23812","article-title":"PPARs in alveolar macrophage biology","volume":"2007","author":"Smith","year":"2007","journal-title":"PPAR Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"549691","DOI":"10.1155\/2015\/549691","article-title":"PPARgamma and the Innate Immune System Mediate the Resolution of Inflammation","volume":"2015","author":"Croasdell","year":"2015","journal-title":"PPAR Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bbalip.2008.04.010","article-title":"Activation of PPARgamma reverses a defect of surfactant synthesis in mice lacking two types of fatty acid binding protein","volume":"1781","author":"Schachtrup","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.4049\/jimmunol.0803504","article-title":"Deletion of PPARg in alveolar macrophages is associated with a Th-1 pulmonary inflammatory response","volume":"182","author":"Malur","year":"2009","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1465-9921-14-7","article-title":"The role of PPARgamma in carbon nanotube-elicited granulomatous lung inflammation","volume":"14","author":"Huizar","year":"2013","journal-title":"Respir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1165\/rcmb.2003-0304RC","article-title":"Peroxisome proliferator-activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis","volume":"30","author":"Culver","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_29","first-page":"93","article-title":"Depressed peroxisome proliferator-activated receptor gamma (PPARgamma) is indicative of severe pulmonary sarcoidosis: Possible involvement of interferon gamma (IFN-gamma)","volume":"23","author":"Barna","year":"2006","journal-title":"Sarcoidosis. Vasc. Diffuse. Lung Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1172\/JCI111852","article-title":"Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis","volume":"75","author":"Robinson","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1365-2249.1991.tb08129.x","article-title":"Detection of endogenous cytokines in sera or in lymph nodes obtained from patients with sarcoidosis","volume":"84","author":"Asano","year":"1991","journal-title":"Clin. Exp. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1164\/rccm.201507-1499OC","article-title":"Interferon-\u03b3-producing Th17.1 Cells are Increased in Sarcoidosis and More Prevalent Than Th1 Cells","volume":"193","author":"Ramstein","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7530","DOI":"10.4049\/jimmunol.172.12.7530","article-title":"Repression of IFN-gamma expression by peroxisome proliferator-activated receptor gamma","volume":"172","author":"Cunard","year":"2004","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"553949","DOI":"10.3389\/fimmu.2020.553949","article-title":"Matrix Metalloproteinase-12 Is Required for Granuloma Progression","volume":"11","author":"Mohan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.bbrc.2018.06.061","article-title":"PPAR-gamma pathways attenuate pulmonary granuloma formation in a carbon nanotube induced murine model of sarcoidosis","volume":"503","author":"McPeek","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/eji.1830270508","article-title":"Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1","volume":"27","author":"Martin","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.4049\/jimmunol.1003626","article-title":"NF-kappaB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages","volume":"186","author":"Zhao","year":"2011","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/MCP.0000000000000301","article-title":"From granuloma to fibrosis: Sarcoidosis associated pulmonary fibrosis","volume":"22","author":"Bonham","year":"2016","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4172\/2157-7439.1000340","article-title":"Exposure to a Mycobacterial Antigen, ESAT-6, Exacerbates Granulomatous and Fibrotic Changes in a Multiwall Carbon Nanotube Model of Chronic Pulmonary Disease","volume":"6","author":"Malur","year":"2015","journal-title":"J. Nanomed. Nanotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Malur, A., Mohan, A., Barrington, R.A., Leffler, N., Malur, A., Muller-Borer, B., Murray, G., Kew, K., Zhou, C., and Russell, J. (2019). PPARgamma Deficiency Exacerbates Fibrotic Response to Mycobacteria Peptide in Murine Sarcoidosis Model. Am. J. Respir. Cell Mol. Biol.","DOI":"10.1164\/ajrccm-conference.2019.199.1_MeetingAbstracts.A2429"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1365-2249.2007.03510.x","article-title":"Multiple Mycobacterium antigens induce interferon-gamma production from sarcoidosis peripheral blood mononuclear cells","volume":"150","author":"Carlisle","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1128\/IAI.00732-06","article-title":"Cellular recognition of Mycobacterium tuberculosis ESAT-6 and KatG peptides in systemic sarcoidosis","volume":"75","author":"Drake","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fang, C., Huang, H., and Xu, Z. (2016). Immunolgical evidence for the role of mycobacteria in sarcoidosis: A meta-analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154716"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.4049\/jimmunol.1200495","article-title":"Systemic analysis of PPARgamma in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity","volume":"189","author":"Gautier","year":"2012","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sanderford, V., Barna, B.P., Barrington, R.A., Malur, A., Mohan, A., Leffler, N., Soliman, E., and Thomassen, M.J. (2020). PPARgamma Deficiency in Carbon Nanotube-elicited Granulomatous Inflammation Promotes a Th17 Response to a Microbial Antigen. J. Nanomed. Nanotechnol., 11.","DOI":"10.35248\/2157-7439.20.11.541"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/MCP.0000000000000498","article-title":"Role of imbalance between Th17 and regulatory T-cells in sarcoidosis","volume":"24","author":"Crouser","year":"2018","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1080\/17476348.2019.1655401","article-title":"New concepts in the pathogenesis of sarcoidosis","volume":"13","author":"Bennett","year":"2019","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"L980","DOI":"10.1152\/ajplung.00234.2005","article-title":"Pulmonary abnormalities due to ABCA1 deficiency in mice","volume":"289","author":"Bates","year":"2005","journal-title":"AJP Lung Cell. Mol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/01.mol.0000226113.89812.bb","article-title":"ATP-binding cassette transporter G1 and lipid homeostasis","volume":"17","author":"Baldan","year":"2006","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1194\/jlr.P700022-JLR200","article-title":"ABCG1 is deficient in alveolar macrophages of GM-CSF knock-out mice and patients with pulmonary alveolar proteinsosis","volume":"48","author":"Thomassen","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1165\/rcmb.2015-0332OC","article-title":"Elevated MicroRNA-33 in Sarcoidosis and a Carbon Nanotube Model of Chronic Granulomatous Disease","volume":"54","author":"Barna","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1194\/jlr.M001651","article-title":"Targeted PPAR{gamma} deficiency in alveolar macrophages disrupts surfactant catabolism","volume":"51","author":"Baker","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1165\/rcmb.2018-0365OC","article-title":"Alveolar Macrophage ABCG1 Deficiency Promotes Pulmonary Granulomatous Inflammation","volume":"61","author":"McPeek","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1465-9921-12-13","article-title":"Lack of cathepsin activities alter or prevent the development of lung granulomas in a mouse model of sarcoidosis","volume":"12","author":"Samokhin","year":"2011","journal-title":"Respir. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1126\/science.1074900","article-title":"Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection","volume":"297","author":"Nguyen","year":"2002","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S1359-6101(03)00055-8","article-title":"The role of osteopontin in lung disease","volume":"14","year":"2003","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1164\/rccm.200803-490OC","article-title":"Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis","volume":"179","author":"Crouser","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.4049\/jimmunol.162.2.1024","article-title":"Osteopontin is associated with T cells in sacroid granulomas and has T cell adhesive and cytokin-like properties in vitro","volume":"162","author":"Chupp","year":"1999","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1755-1536-4-10","article-title":"Immune response CC chemokines CCL2 and CCL5 are associated with pulmonary sarcoidosis","volume":"4","author":"Palchevskiy","year":"2011","journal-title":"Fibrogenesis. Tissue Repair."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23858","DOI":"10.3390\/ijms141223858","article-title":"Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar macrophage m1 activation","volume":"14","author":"Barna","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.chest.2017.11.030","article-title":"The Pathogenesis of Pulmonary Sarcoidosis and Implications for Treatment","volume":"153","author":"Patterson","year":"2018","journal-title":"Chest"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1743-8977-8-24","article-title":"Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL\/6 mice","volume":"8","author":"Wang","year":"2011","journal-title":"Part. Fibre. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1084\/jem.187.4.601","article-title":"Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice","volume":"187","author":"Lu","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1183\/09031936.03.00083002","article-title":"Alveolar macrophages are the main source for tumour necrosis factor-alpha in patients with sarcoidosis","volume":"21","author":"Fehrenbach","year":"2003","journal-title":"Eur. Respir. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1046\/j.1365-2249.2000.01365.x","article-title":"Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveolar CD4+ and CD8+ T cells","volume":"122","author":"Prasse","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1172\/JCI57275","article-title":"Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis","volume":"121","author":"Rayner","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Besnard, V., and Jeny, F. (2020). Models Contribution to the Understanding of Sarcoidosis Pathogenesis: \u201cAre There Good Models of Sarcoidosis?\u201d. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082445"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3705\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:58:10Z","timestamp":1760363890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,2]]},"references-count":67,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073705"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073705","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,2]]}}}