
α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review)
- Authors:
- Tiantian Wang
- Peimeng Shuai
- Qingyu Wang
- Caimao Guo
- Shuqi Huang
- Yuanyuan Li
- Wenyu Wu
- Lan Yi
-
Affiliations: Hengyang Key Laboratory of Cellular Stress Biology, Institute of Cytology and Genetics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, P.R. China, Hengyang Key Laboratory of Cellular Stress Biology, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, P.R. China - Published online on: February 24, 2025 https://doi.org/10.3892/mmr.2025.13472
- Article Number: 107
-
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
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Sabina J and Tobias W: Augmentation therapy with alpha1-antitrypsin: Novel perspectives. Cardiovasc Hematol Disord Drug Targets. 13:90–98. 2013. View Article : Google Scholar : PubMed/NCBI | |
Lechowicz U, Rudzinski S, Jezela-Stanek A, Janciauskiene S and Chorostowska-Wynimko J: Post-translational modifications of circulating alpha-1-antitrypsin protein. Int J Mol Sci. 21:91872020. View Article : Google Scholar : PubMed/NCBI | |
Santangelo S, Scarlata S, Poeta ML, Bialas AJ, Paone G and Incalzi RA: Alpha-1 antitrypsin deficiency: Current perspective from genetics to diagnosis and therapeutic approaches. Curr Med Chem. 24:65–90. 2017. View Article : Google Scholar : PubMed/NCBI | |
Haq I, Irving JA, Saleh AD, Dron L, Regan-Mochrie GL, Motamedi-Shad N, Hurst JR, Gooptu B and Lomas DA: Deficiency mutations of alpha-1 antitrypsin. Effects on folding, function, and polymerization. Am J Respir Cell Mol Biol. 54:71–80. 2016. View Article : Google Scholar : PubMed/NCBI | |
van't Wout EF, van Schadewijk A, Savage ND, Stolk J and Hiemstra PS: α1-Antitrypsin production by proinflammatory and antiinflammatory macrophages and dendritic cells. Am J Respir Cell Mol Biol. 46:607–613. 2012. View Article : Google Scholar : PubMed/NCBI | |
de Serres F and Blanco I: Role of alpha-1 antitrypsin in human health and disease. J Intern Med. 276:311–335. 2014. View Article : Google Scholar : PubMed/NCBI | |
Rahaghi FF and Miravitlles M: Long-term clinical outcomes following treatment with alpha 1-proteinase inhibitor for COPD associated with alpha-1 antitrypsin deficiency: A look at the evidence. Respir Res. 18:1052017. View Article : Google Scholar : PubMed/NCBI | |
Stockley RA: Alpha1-antitrypsin review. Clin Chest Med. 35:39–50. 2014. View Article : Google Scholar : PubMed/NCBI | |
Song S: Alpha-1 antitrypsin therapy for autoimmune disorders. Chronic Obstr Pulm Dis. 5:289–301. 2018.PubMed/NCBI | |
Serban KA, Petrusca DN, Mikosz A, Poirier C, Lockett AD, Saint L, Justice MJ, Twigg HL III, Campos MA and Petrache I: Alpha-1 antitrypsin supplementation improves alveolar macrophages efferocytosis and phagocytosis following cigarette smoke exposure. PLoS One. 12:e01760732017. View Article : Google Scholar : PubMed/NCBI | |
Jiang S, Liu G, Yuan H, Xu E, Xia W, Zhang X, Liu J and Gao L: Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol. Sci Rep. 11:14542021. View Article : Google Scholar : PubMed/NCBI | |
Yarmohammadi ME, Hassan ZM, Mostafaie A, Ebtekar M, Yaraee R, Pourfarzam S, Jalali-Nadoushan M, Faghihzadeh S, Vaez-Mahdavi MR, Soroush MR, et al: Salivary levels of secretary IgA, C5a and alpha 1-antitrypsin in sulfur mustard exposed patients 20 years after the exposure, sardasht-Iran cohort study (SICS). Int Immunopharmacol. 17:952–957. 2013. View Article : Google Scholar : PubMed/NCBI | |
Burgess JL, Kurzius-Spencer M, Poplin GS, Littau SR, Kopplin MJ, Stürup S, Boitano S and Clark Lantz R: Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin. J Expo Sci Environ Epidemiol. 24:150–155. 2014. View Article : Google Scholar : PubMed/NCBI | |
Yi L, Cui J, Hu N, Li L, Chen Y, Mu H, Yin J, Wei S, Gong Y, Wei Y, et al: iTRAQ-based proteomic profiling of potential biomarkers in rat serum for uranium tailing suspension intratracheal instillation. J Proteome Res. 20:995–1004. 2021. View Article : Google Scholar : PubMed/NCBI | |
Veith M, Tüffers J, Peychev E, Klemmer A, Kotke V, Janciauskiene S, Wilhelm S, Bals R, Koczulla AR, Vogelmeier CF and Greulich T: The distribution of alpha-1 antitrypsin genotypes between patients with COPD/emphysema, asthma and bronchiectasis. Int J Chron Obstruct Pulmon Dis. 15:2827–2836. 2020. View Article : Google Scholar : PubMed/NCBI | |
Alam S, Li Z, Atkinson C, Jonigk D, Janciauskiene S and Mahadeva R: Z α1-antitrypsin confers a proinflammatory phenotype that contributes to chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 189:909–931. 2014. View Article : Google Scholar : PubMed/NCBI | |
Ordóñez A, Snapp EL, Tan L, Miranda E, Marciniak SJ and Lomas DA: Endoplasmic reticulum polymers impair luminal protein mobility and sensitize to cellular stress in alpha1-antitrypsin deficiency. Hepatology. 57:2049–2060. 2013. View Article : Google Scholar : PubMed/NCBI | |
Giri Rao VVH and Gosavi S: On the folding of a structurally complex protein to its metastable active state. Proc Natl Acad Sci USA. 115:1998–2003. 2018. View Article : Google Scholar : PubMed/NCBI | |
Ordóñez A, Harding HP, Marciniak SJ and Ron D: Cargo receptor-assisted endoplasmic reticulum export of pathogenic α1-antitrypsin polymers. Cell Rep. 35:1091442021. View Article : Google Scholar : PubMed/NCBI | |
Ronzoni R, Berardelli R, Medicina D, Sitia R, Gooptu B and Fra AM: Aberrant disulphide bonding contributes to the ER retention of alpha1-antitrypsin deficiency variants. Hum Mol Genet. 25:642–650. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lockett AD: Alpha-1 antitrypsin transcytosis and secretion. Methods Mol Biol. 1639:173–184. 2017. View Article : Google Scholar : PubMed/NCBI | |
Lockett AD, Brown MB, Santos-Falcon N, Rush NI, Oueini H, Oberle AJ, Bolanis E, Fragoso MA, Petrusca DN, Serban KA, et al: Active trafficking of alpha 1 antitrypsin across the lung endothelium. PLoS One. 9:e939792014. View Article : Google Scholar : PubMed/NCBI | |
Kim M, Cai Q and Oh Y: Therapeutic potential of alpha-1 antitrypsin in human disease. Ann Pediatr Endocrinol Metab. 23:131–135. 2018. View Article : Google Scholar : PubMed/NCBI | |
Schuster R, Motola-Kalay N, Baranovski BM, Bar L, Tov N, Stein M, Lewis EC, Ayalon M and Sagiv Y: Distinct anti-inflammatory properties of alpha1-antitrypsin and corticosteroids reveal unique underlying mechanisms of action. Cell Immunol. 356:1041772020. View Article : Google Scholar : PubMed/NCBI | |
Ostermann L, Maus R, Stolper J, Schütte L, Katsarou K, Tumpara S, Pich A, Mueller C, Janciauskiene S, Welte T and Maus UA: Alpha-1 antitrypsin deficiency impairs lung antibacterial immunity in mice. JCI Insight. 6:e1408162021. View Article : Google Scholar : PubMed/NCBI | |
Serban KA and Petrache I: alpha-1 antitrypsin and lung cell apoptosis. Ann Am Thorac Soc. 13 (Suppl 2):S146–S149. 2016.PubMed/NCBI | |
Han L, Wu X, Wang O, Luan X, Velander WH, Aynardi M, Halstead ES, Bonavia AS, Jin R, Li G, et al: Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution. Theranostics. 13:2843–2862. 2023. View Article : Google Scholar : PubMed/NCBI | |
Baraldo S, Turato G, Lunardi F, Bazzan E, Schiavon M, Ferrarotti I, Molena B, Cazzuffi R, Damin M, Balestro E, et al: Immune activation in α1-antitrypsin-deficiency emphysema. Beyond the protease-antiprotease paradigm. Am J Respir Crit Care Med. 191:402–409. 2015. View Article : Google Scholar : PubMed/NCBI | |
Jonigk D, Al-Omari M, Maegel L, Müller M, Izykowski N, Hong J, Hong K, Kim SH, Dorsch M, Mahadeva R, et al: Anti-inflammatory and immunomodulatory properties of α1-antitrypsin without inhibition of elastase. Proc Natl Acad Sci USA. 110:15007–15012. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ehlers MR: Immune-modulating effects of alpha-1 antitrypsin. Biol Chem. 395:1187–1193. 2014. View Article : Google Scholar : PubMed/NCBI | |
Tawara I, Sun Y, Lewis EC, Toubai T, Evers R, Nieves E, Azam T, Dinarello CA and Reddy P: Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation. Proc Natl Acad Sci USA. 109:564–569. 2012. View Article : Google Scholar : PubMed/NCBI | |
Blas-García A and Apostolova N: Novel therapeutic approaches to liver fibrosis based on targeting oxidative stress. Antioxidants (Basel). 12:15672023. View Article : Google Scholar : PubMed/NCBI | |
Feng Y, Xu J, Zhou Q, Wang R, Liu N, Wu Y, Yuan H and Che H: Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress. Front Physiol. 7:1762016. View Article : Google Scholar : PubMed/NCBI | |
Chapman KR, Chorostowska-Wynimko J, Koczulla AR, Ferrarotti I and McElvaney NG: Alpha 1 antitrypsin to treat lung disease in alpha 1 antitrypsin deficiency: Recent developments and clinical implications. Int J Chron Obstruct Pulmon Dis. 13:419–432. 2018. View Article : Google Scholar : PubMed/NCBI | |
Janciauskiene S and Welte T: Well-known and less well-known functions of alpha-1 antitrypsin. its role in chronic obstructive pulmonary disease and other disease developments. Ann Am Thorac Soc. 13 (Suppl 4):S280–S288. 2016. View Article : Google Scholar : PubMed/NCBI | |
Cosio MG, Bazzan E, Rigobello C, Tinè M, Turato G, Baraldo S and Saetta M: Alpha-1 antitrypsin deficiency: beyond the protease/antiprotease paradigm. Ann Am Thorac Soc. 13 (Suppl 4):S305–S310. 2016. View Article : Google Scholar : PubMed/NCBI | |
Stockley RA: The multiple facets of alpha-1-antitrypsin. Ann Transl Med. 3:1302015.PubMed/NCBI | |
Schwarz N, Tumpara S, Wrenger S, Ercetin E, Hamacher J, Welte T and Janciauskiene S: Alpha1-antitrypsin protects lung cancer cells from staurosporine-induced apoptosis: The role of bacterial lipopolysaccharide. Sci Rep. 10:95632020. View Article : Google Scholar : PubMed/NCBI | |
Meghadri SH, Martinez-Delgado B, Ostermann L, Gomez-Mariano G, Perez-Luz S, Tumpara S, Wrenger S, DeLuca DS, Maus UA, Welte T and Janciauskiene S: Loss of Serpina1 in mice leads to altered gene expression in inflammatory and metabolic pathways. Int J Mol Sci. 23:104252022. View Article : Google Scholar : PubMed/NCBI | |
Stolk J, Tov N, Chapman KR, Fernandez P, MacNee W, Hopkinson NS, Piitulainen E, Seersholm N, Vogelmeier CF, Bals R, et al: Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD. Eur Respir J. 54:19006732019. View Article : Google Scholar : PubMed/NCBI | |
McElvaney NG: Alpha-1 antitrypsin therapy in cystic fibrosis and the lung disease associated with alpha-1 antitrypsin deficiency. Ann Am Thorac Soc. 13 (Suppl 2):S191–S196. 2016.PubMed/NCBI | |
Demir N, Erçen Diken Ö, Karabulut HG, Karnak D and Kayacan O: Alpha-1 antitrypsin levels and polymorphisms in interstitial lung diseases. Turk J Med Sci. 47:476–482. 2017. View Article : Google Scholar : PubMed/NCBI | |
Oriano M, Amati F, Gramegna A, De Soyza A, Mantero M, Sibila O, Chotirmall SH, Voza A, Marchisio P, Blasi F and Aliberti S: Protease-antiprotease imbalance in bronchiectasis. Int J Mol Sci. 22:59962021. View Article : Google Scholar : PubMed/NCBI | |
Murphy MP, McEnery T, McQuillan K, McElvaney OF, McElvaney OJ, Landers S, Coleman O, Bussayajirapong A, Hawkins P, Henry M, et al: α1 Antitrypsin therapy modulates the neutrophil membrane proteome and secretome. Eur Respir J. 55:19016782020. View Article : Google Scholar : PubMed/NCBI | |
Ritzmann F, Chitirala P, Krüger N, Hoffmann M, Zuo W, Lammert F, Smola S, Tov N, Alagem N, Lepper PM, et al: Therapeutic application of alpha-1 antitrypsin in COVID-19. Am J Respir Crit Care Med. 204:224–227. 2021. View Article : Google Scholar : PubMed/NCBI | |
Yang C, Keshavjee S and Liu M: Alpha-1 antitrypsin for COVID-19 treatment: Dual role in antiviral infection and anti-inflammation. Front Pharmacol. 11:6153982020. View Article : Google Scholar : PubMed/NCBI | |
Li Y, Miao L, Yu M, Shi M, Wang Y, Yang J, Xiao Y and Cai H: α1-Antitrypsin promotes lung adenocarcinoma metastasis through upregulating fibronectin expression. Int J Oncol. 50:1955–1964. 2017. View Article : Google Scholar : PubMed/NCBI | |
Khodayari N, Wang RL, Oshins R, Lu Y, Millett M, Aranyos AM, Mostofizadeh S, Scindia Y, Flagg TO and Brantly M: The mechanism of mitochondrial injury in alpha-1 antitrypsin deficiency mediated liver disease. Int J Mol Sci. 22:132552021. View Article : Google Scholar : PubMed/NCBI | |
Tanash HA and Piitulainen E: Liver disease in adults with severe alpha-1-antitrypsin deficiency. J Gastroenterol. 54:541–548. 2019. View Article : Google Scholar : PubMed/NCBI | |
Franciosi AN, Ralph J, O'Farrell NJ, Buckley C, Gulmann C, O'Kane M, Carroll TP and McElvaney NG: Alpha-1 antitrypsin deficiency-associated panniculitis. J Am Acad Dermatol. 87:825–832. 2022. View Article : Google Scholar : PubMed/NCBI | |
Wang Q, Du J, Yu P, Bai B, Zhao Z, Wang S, Zhu J, Feng Q, Gao Y, Zhao Q and Liu C: Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis. Sci Rep. 5:178332015. View Article : Google Scholar : PubMed/NCBI | |
Yu Y, Rubin AG, Gee S, Banker S and Kim CN: Ulcerative panniculitis with fevers and pleural effusions: A unique case of α1-antitrypsin deficiency. JAAD Case Rep. 1:1–2. 2014. View Article : Google Scholar : PubMed/NCBI | |
Jedicke N, Struever N, Aggrawal N, Welte T, Manns MP, Malek NP, Zender L, Janciauskiene S and Wuestefeld T: α-1-antitrypsin inhibits acute liver failure in mice. Hepatology. 59:2299–2308. 2014. View Article : Google Scholar : PubMed/NCBI | |
Elshikha AS, Lu Y, Chen MJ, Akbar M, Zeumer L, Ritter A, Elghamry H, Mahdi MA, Morel L and Song S: Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus. PLoS One. 11:e01565832016. View Article : Google Scholar : PubMed/NCBI | |
Pervakova MY, Emanuel VL, Titova ON, Lapin SV, Mazurov VI, Belyaeva IB, Chudinov AL, Blinova TV and Surkova EA: The diagnostic value of alpha-1-antitrypsin phenotype in patients with granulomatosis with polyangiitis. Int J Rheumatol. 2016:78314102016. View Article : Google Scholar : PubMed/NCBI | |
Mota A, Sahebghadam Lotfi A, Jamshidi AR and Najavand S: Alpha 1-antitrypsin activity is markedly decreased in Wegener's granulomatosis. Rheumatol Int. 34:553–558. 2014. View Article : Google Scholar : PubMed/NCBI | |
Mauro AG, Mezzaroma E, Marchetti C, Narayan P, Del Buono MG, Capuano M, Prestamburgo A, Catapano S, Salloum FN, Abbate A and Toldo S: A preclinical translational study of the cardioprotective effects of plasma-derived alpha-1 anti-trypsin in acute myocardial infarction. J Cardiovasc Pharmacol. 69:273–278. 2017. View Article : Google Scholar : PubMed/NCBI | |
Toldo S, Mauro AG, Marchetti C, Rose SW, Mezzaroma E, Van Tassell BW, Kim S, Dinarello CA and Abbate A: Recombinant human alpha-1 antitrypsin-Fc fusion protein reduces mouse myocardial inflammatory injury after ischemia-reperfusion independent of elastase inhibition. J Cardiovasc Pharmacol. 68:27–32. 2016. View Article : Google Scholar : PubMed/NCBI | |
Lockett AD, Petrusca DN, Justice MJ, Poirier C, Serban KA, Rush NI, Kamocka M, Predescu D, Predescu S and Petrache I: Scavenger receptor class B, type I-mediated uptake of A1AT by pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol. 309:L425–L434. 2015. View Article : Google Scholar : PubMed/NCBI | |
Zhou T, Huang Z, Zhu X, Sun X, Liu Y, Cheng B, Li M, Liu Y, He C and Liu X: Alpha-1 antitrypsin attenuates M1 microglia-mediated neuroinflammation in retinal degeneration. Front Immunol. 9:12022018. View Article : Google Scholar : PubMed/NCBI | |
Ebrahimi T, Rust M, Kaiser SN, Slowik A, Beyer C, Koczulla AR, Schulz JB, Habib P and Bach JP: α1-Antitrypsin mitigates NLRP3-inflammasome activation in amyloid β1-42-stimulated murine astrocytes. J Neuroinflammation. 15:2822018. View Article : Google Scholar : PubMed/NCBI | |
Park SS, Rodriguez Ortega R, Agudelo CW, Perez Perez J, Perez Gandara B, Garcia-Arcos I, McCarthy C and Geraghty P: Therapeutic potential of alpha-1 antitrypsin in type 1 and type 2 diabetes mellitus. Medicina (Kaunas). 57:3972021. View Article : Google Scholar : PubMed/NCBI | |
Fleixo-Lima G, Ventura H, Medini M, Bar L, Strauss P and Lewis EC: Mechanistic evidence in support of alpha1-antitrypsin as a therapeutic approach for type 1 diabetes. J Diabetes Sci Technol. 8:1193–1203. 2014. View Article : Google Scholar : PubMed/NCBI | |
Kalis M, Kumar R, Janciauskiene S, Salehi A and Cilio CM: α 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated apoptosis in pancreatic β-cells. Islets. 2:185–189. 2010. View Article : Google Scholar : PubMed/NCBI | |
Liu W and Wang Y: Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration. J Orthop Surg Res. 16:5162021. View Article : Google Scholar : PubMed/NCBI | |
Pérez-Holanda S, Blanco I, Menéndez M and Rodrigo L: Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls. BMC Cancer. 14:3552014. View Article : Google Scholar : PubMed/NCBI | |
Tountas Y, Sparos L, Theodoropoulos C and Trichopoulos D: Alpha 1-antitrypsin and cancer of the pancreas. Digestion. 31:37–40. 1985. View Article : Google Scholar : PubMed/NCBI | |
Vasishta A, Baker PR, Preece PE, Wood RA and Cuschieri A: Serum proteinase-like peptidase activities and proteinase inhibitors in women with breast disease. Eur J Cancer Clin Oncol. 20:197–202. 1984. View Article : Google Scholar : PubMed/NCBI | |
Warwas M, Gerber J and Pietkiewicz A: Haptoglobin and proteinase inhibitors in the blood serum of women with inflammatory, benign and neoplastic lesions of the ovary. Neoplasma. 33:79–84. 1986.PubMed/NCBI | |
Janciauskiene S, Wrenger S, Günzel S, Gründing AR, Golpon H and Welte T: Potential roles of acute phase proteins in cancer: Why do cancer cells produce or take up exogenous acute phase protein alpha1-antitrypsin? Front Oncol. 11:6220762021. View Article : Google Scholar : PubMed/NCBI | |
Hsu PI, Chen CH, Hsiao M, Wu DC, Lin CY, Lai KH and Lu PJ: Diagnosis of gastric malignancy using gastric juice alpha1-antitrypsin. Cancer Epidemiol Biomarkers Prev. 19:405–411. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wu W, Juan WC, Liang CR, Yeoh KG, So J and Chung MC: S100A9, GIF and AAT as potential combinatorial biomarkers in gastric cancer diagnosis and prognosis. Proteomics Clin Appl. 6:152–162. 2012. View Article : Google Scholar : PubMed/NCBI | |
Geramizadeh B, Jowkar Z, Karami L, Masoumpour M, Mehrabi S and Ghayoumi MA: Alpha-1 antitrypsin deficiency in Iranian patients with chronic obstructive pulmonary disease. Iran Red Crescent Med J. 15:e75082013. View Article : Google Scholar : PubMed/NCBI | |
Matamala N, Lara B, Gomez-Mariano G, Martínez S, Retana D, Fernandez T, Silvestre RA, Belmonte I, Rodriguez-Frias F, Vilar M, et al: Characterization of novel missense variants of SERPINA1 gene causing alpha-1 antitrypsin deficiency. Am J Respir Cell Mol Biol. 58:706–716. 2018. View Article : Google Scholar : PubMed/NCBI | |
Foil KE: Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency. Ther Adv Chronic Dis (12 Suppl). 204062232110159542021. View Article : Google Scholar : PubMed/NCBI | |
Tsutsui Y, Dela Cruz R and Wintrode PL: Folding mechanism of the metastable serpin α1-antitrypsin. Proc Natl Acad Sci USA. 109:4467–4472. 2012. View Article : Google Scholar : PubMed/NCBI | |
Marciniak SJ, Ordóñez A, Dickens JA, Chambers JE, Patel V, Dominicus CS and Malzer E: New concepts in alpha-1 antitrypsin deficiency disease mechanisms. Ann Am Thorac Soc. 13 (Suppl 4):S289–S296. 2016. View Article : Google Scholar : PubMed/NCBI | |
Börner FR, Lechowicz U, Wrenger S, Martinez-Delgado B, Olejnicka B, Welte T, Chorostowska-Wynimko J, Kiehntopf M and Janciauskiene S: Plasma levels of α1-antitrypsin-derived C-terminal peptides in PiMM and PiZZ COPD patients. ERJ Open Res. 9:00329–2023. 2023. View Article : Google Scholar : PubMed/NCBI | |
Fra AM, Gooptu B, Ferrarotti I, Miranda E, Scabini R, Ronzoni R, Benini F, Corda L, Medicina D, Luisetti M and Schiaffonati L: Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization. PLoS One. 7:e384052012. View Article : Google Scholar : PubMed/NCBI | |
Salahuddin P: Genetic variants of alpha1-antitrypsin. Curr Protein Pept Sci. 11:101–117. 2010. View Article : Google Scholar : PubMed/NCBI | |
Karatas E and Bouchecareilh M: Alpha 1-antitrypsin deficiency: A disorder of proteostasis-mediated protein folding and trafficking pathways. Int J Mol Sci. 21:14932020. View Article : Google Scholar : PubMed/NCBI | |
Miranda E, Ferrarotti I, Berardelli R, Laffranchi M, Cerea M, Gangemi F, Haq I, Ottaviani S, Lomas DA, Irving JA and Fra A: The pathological Trento variant of alpha-1-antitrypsin (E75V) shows nonclassical behaviour during polymerization. FEBS J. 284:2110–2126. 2017. View Article : Google Scholar : PubMed/NCBI | |
Laffranchi M, Berardelli R, Ronzoni R, Lomas DA and Fra A: Heteropolymerization of α-1-antitrypsin mutants in cell models mimicking heterozygosity. Hum Mol Genet. 27:1785–1793. 2018. View Article : Google Scholar : PubMed/NCBI | |
Laffranchi M, Elliston ELK, Gangemi F, Berardelli R, Lomas DA, Irving JA and Fra A: Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population. PLoS One. 14:e02069552019. View Article : Google Scholar : PubMed/NCBI | |
Bergin DA, Reeves EP, Hurley K, Wolfe R, Jameel R, Fitzgerald S and McElvaney NG: The circulating proteinase inhibitor α-1 antitrypsin regulates neutrophil degranulation and autoimmunity. Sci Transl Med. 6:217ra12014. View Article : Google Scholar : PubMed/NCBI | |
Hawkins P, McEnery T, Gabillard-Lefort C, Bergin DA, Alfawaz B, Shutchaidat V, Meleady P, Henry M, Coleman O, Murphy M, et al: In vitro and in vivo modulation of NADPH oxidase activity and reactive oxygen species production in human neutrophils by α1-antitrypsin. ERJ Open Res. 7:00234–2021. 2021. View Article : Google Scholar : PubMed/NCBI | |
Voynow JA and Shinbashi M: Neutrophil elastase and chronic lung disease. Biomolecules. 11:10652021. View Article : Google Scholar : PubMed/NCBI | |
Miravitlles M: Alpha-1-antitrypsin and other proteinase inhibitors. Curr Opin Pharmacol. 12:309–314. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hurley K, Lacey N, O'Dwyer CA, Bergin DA, McElvaney OJ, O'Brien ME, McElvaney OF, Reeves EP and McElvaney NG: Alpha-1 antitrypsin augmentation therapy corrects accelerated neutrophil apoptosis in deficient individuals. J Immunol. 193:3978–3991. 2014. View Article : Google Scholar : PubMed/NCBI | |
O'Dwyer CA, O'Brien ME, Wormald MR, White MM, Banville N, Hurley K, McCarthy C, McElvaney NG and Reeves EP: The BLT1 inhibitory function of α-1 antitrypsin augmentation therapy disrupts leukotriene B4 neutrophil signaling. J Immunol. 195:3628–3641. 2015. View Article : Google Scholar : PubMed/NCBI | |
McCarthy C, Reeves EP and McElvaney NG: The role of neutrophils in alpha-1 antitrypsin deficiency. Ann Am Thorac Soc. 13 (Suppl 4):S297–S304. 2016. View Article : Google Scholar : PubMed/NCBI | |
Fazleen A and Wilkinson T: The emerging role of proteases in α1-antitrypsin deficiency and beyond. ERJ Open Res. 7:00494–2021. 2021. View Article : Google Scholar : PubMed/NCBI | |
O'Brien ME, Murray G, Gogoi D, Yusuf A, McCarthy C, Wormald MR, Casey M, Gabillard-Lefort C, McElvaney NG and Reeves EP: A review of alpha-1 antitrypsin binding partners for immune regulation and potential therapeutic application. Int J Mol Sci. 23:24412022. View Article : Google Scholar : PubMed/NCBI | |
Joosten LA, Crişan TO, Azam T, Cleophas MC, Koenders MI, van de Veerdonk FL, Netea MG, Kim S and Dinarello CA: Alpha-1-anti-trypsin-Fc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1β and by the induction of endogenous IL-1Ra. Ann Rheum Dis. 75:1219–1227. 2016. View Article : Google Scholar : PubMed/NCBI | |
Agné A, Richter K, Padberg W, Janciauskiene S and Grau V: Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β. Pulm Pharmacol Ther. 68:1020202021. View Article : Google Scholar : PubMed/NCBI | |
Siebers K, Fink B, Zakrzewicz A, Agné A, Richter K, Konzok S, Hecker A, Zukunft S, Küllmar M, Klein J, et al: Alpha-1 antitrypsin inhibits ATP-mediated release of interleukin-1β via CD36 and nicotinic acetylcholine receptors. Front Immunol. 9:8772018. View Article : Google Scholar : PubMed/NCBI | |
Bergin DA, Reeves EP, Meleady P, Henry M, McElvaney OJ, Carroll TP, Condron C, Chotirmall SH, Clynes M, O'Neill SJ and McElvaney NG: α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin Invest. 120:4236–4250. 2010. View Article : Google Scholar : PubMed/NCBI | |
Lee J, Lu Y, Oshins R, West J, Moneypenny CG, Han K and Brantly ML: Alpha 1 antitrypsin-deficient macrophages have impaired efferocytosis of apoptotic neutrophils. Front Immunol. 11:5744102020. View Article : Google Scholar : PubMed/NCBI | |
Lockett AD, Kimani S, Ddungu G, Wrenger S, Tuder RM, Janciauskiene SM and Petrache I: α1-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-α. Am J Respir Cell Mol Biol. 49:143–150. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zhukovsky N, Silvano M, Filloux T, Gonzalez S and Krause KH: Alpha-1 antitrypsin reduces disease progression in a mouse model of charcot-marie-tooth type 1A: A role for decreased inflammation and ADAM-17 inhibition. Int J Mol Sci. 23:74052022. View Article : Google Scholar : PubMed/NCBI | |
Abecassis A, Schuster R, Shahaf G, Ozeri E, Green R, Ochayon DE, Rider P and Lewis EC: α1-Antitrypsin increases interleukin-1 receptor antagonist production during pancreatic islet graft transplantation. Cell Mol Immunol. 11:377–386. 2014. View Article : Google Scholar : PubMed/NCBI | |
Ozeri E, Mizrahi M, Shahaf G and Lewis EC: α-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol. 189:146–153. 2012. View Article : Google Scholar : PubMed/NCBI | |
Wang J, Sun Z, Gou W, Adams DB, Cui W, Morgan KA, Strange C and Wang H: α-1 antitrypsin enhances islet engraftment by suppression of instant blood-mediated inflammatory reaction. Diabetes. 66:970–980. 2017. View Article : Google Scholar : PubMed/NCBI | |
Mukherjee A, Hidvegi T, Araya P, Ewing M, Stolz DB and Perlmutter DH: NFκB mitigates the pathological effects of misfolded α1-antitrypsin by activating autophagy and an integrated program of proteostasis mechanisms. Cell Death Differ. 26:455–469. 2019. View Article : Google Scholar : PubMed/NCBI | |
Pastore N, Blomenkamp K, Annunziata F, Piccolo P, Mithbaokar P, Maria Sepe R, Vetrini F, Palmer D, Ng P, Polishchuk E, et al: Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency. EMBO Mol Med. 5:397–412. 2013. View Article : Google Scholar : PubMed/NCBI | |
Rivas M, Gupta G, Costanzo L, Ahmed H, Wyman AE and Geraghty P: Senescence: Pathogenic driver in chronic obstructive pulmonary disease. Medicina (Kaunas). 58:8172022. View Article : Google Scholar : PubMed/NCBI | |
Saferali A, Lee J, Sin DD, Rouhani FN, Brantly ML and Sandford AJ: Longer telomere length in COPD patients with α1-antitrypsin deficiency independent of lung function. PLoS One. 9:e956002014. View Article : Google Scholar : PubMed/NCBI | |
Escribano A, Pastor S, Reula A, Castillo S, Vicente S, Sanz F, Casas F, Torres M, Fernández-Fabrellas E, Codoñer-Franch P and Dasí F: Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency. Eur Respir J. 48:350–358. 2016. View Article : Google Scholar : PubMed/NCBI | |
Hurley K, Reeves EP, Carroll TP and McElvaney NG: Tumor necrosis factor-α driven inflammation in alpha-1 antitrypsin deficiency: A new model of pathogenesis and treatment. Expert Rev Respir Med. 10:207–222. 2016. View Article : Google Scholar : PubMed/NCBI | |
Li Z, Alam S, Wang J, Sandstrom CS, Janciauskiene S and Mahadeva R: Oxidized {alpha}1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: Potential role in emphysema. Am J Physiol Lung Cell Mol Physiol. 297:L388–L400. 2009. View Article : Google Scholar : PubMed/NCBI | |
Subramaniyam D, Glader P, von Wachenfeldt K, Burneckiene J, Stevens T and Janciauskiene S: C-36 peptide, a degradation product of alpha1-antitrypsin, modulates human monocyte activation through LPS signaling pathways. Int J Biochem Cell Biol. 38:563–575. 2006. View Article : Google Scholar : PubMed/NCBI | |
Antonsson A and Persson JL: Induction of apoptosis by staurosporine involves the inhibition of expression of the major cell cycle proteins at the G(2)/m checkpoint accompanied by alterations in Erk and Akt kinase activities. Anticancer Res. 29:2893–2898. 2009.PubMed/NCBI | |
Campos MA, Geraghty P, Holt G, Mendes E, Newby PR, Ma S, Luna-Diaz LV, Turino GM and Stockley RA: The biological effects of double-dose alpha-1 antitrypsin augmentation therapy. A pilot clinical trial. Am J Respir Crit Care Med. 200:318–326. 2019. View Article : Google Scholar : PubMed/NCBI | |
Hunt JM and Tuder R: Alpha 1 anti-trypsin: One protein, many functions. Curr Mol Med. 12:827–835. 2012. View Article : Google Scholar : PubMed/NCBI | |
Berman R, Jiang D, Wu Q and Chu HW: α1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke. Int J Chron Obstruct Pulmon Dis. 11:1279–1286. 2016. View Article : Google Scholar : PubMed/NCBI | |
Mehta AJ, Thun GA, Imboden M, Ferrarotti I, Keidel D, Künzli N, Kromhout H, Miedinger D, Phuleria H, Rochat T, et al: Interactions between SERPINA1 PiMZ genotype, occupational exposure and lung function decline. Occup Environ Med. 71:234–240. 2014. View Article : Google Scholar : PubMed/NCBI | |
Wrześniak M, Kepinska M, Królik M and Milnerowicz H: The influence of tobacco smoke on protein and metal levels in the serum of women during pregnancy. PLoS One. 11:e01613422016. View Article : Google Scholar : PubMed/NCBI | |
Pemberton PA, Kobayashi D, Wilk BJ, Henstrand JM, Shapiro SD and Barr PJ: Inhaled recombinant alpha 1-antitrypsin ameliorates cigarette smoke-induced emphysema in the mouse. COPD. 3:101–108. 2006. View Article : Google Scholar : PubMed/NCBI | |
Molloy K, Hersh CP, Morris VB, Carroll TP, O'Connor CA, Lasky-Su JA, Greene CM, O'Neill SJ, Silverman EK and McElvaney NG: Clarification of the risk of chronic obstructive pulmonary disease in α1-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med. 189:419–427. 2014. View Article : Google Scholar : PubMed/NCBI | |
Stearns K, Goldklang M, Xiao R, Zelonina T, Blomenkamp K, Teckman J and D'Armiento JM: Knockdown of alpha-1 antitrypsin with antisense oligonucleotide does not exacerbate smoke induced lung injury. PLoS One. 16:e02460402021. View Article : Google Scholar : PubMed/NCBI | |
Rangaraju M and Turner AM: Why is disease penetration so variable in alpha-1 antitrypsin deficiency? The contribution of environmental factors. Chronic Obstr Pulm Dis. 7:280–289. 2020.PubMed/NCBI | |
Churg A, Wang X, Wang RD, Meixner SC, Pryzdial EL and Wright JL: Alpha1-antitrypsin suppresses TNF-alpha and MMP-12 production by cigarette smoke-stimulated macrophages. Am J Respir Cell Mol Biol. 37:144–151. 2007. View Article : Google Scholar : PubMed/NCBI | |
Thun GA, Ferrarotti I, Imboden M, Rochat T, Gerbase M, Kronenberg F, Bridevaux PO, Zemp E, Zorzetto M, Ottaviani S, et al: SERPINA1 PiZ and PiS heterozygotes and lung function decline in the SAPALDIA cohort. PLoS One. 7:e427282012. View Article : Google Scholar : PubMed/NCBI | |
Khodayari N, Oshins R, Mehrad B, Lascano JE, Qiang X, West JR, Holliday LS, Lee J, Wiesemann G, Eydgahi S and Brantly M: Cigarette smoke exposed airway epithelial cell-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency. Respir Res. 23:2322022. View Article : Google Scholar : PubMed/NCBI | |
Al Ashry HS and Strange C: COPD in individuals with the PiMZ alpha-1 antitrypsin genotype. Eur Respir Rev. 26:1700682017. View Article : Google Scholar : PubMed/NCBI | |
Geraghty P, Eden E, Pillai M, Campos M, McElvaney NG and Foronjy RF: α1-Antitrypsin activates protein phosphatase 2A to counter lung inflammatory responses. Am J Respir Crit Care Med. 190:1229–1242. 2014. View Article : Google Scholar : PubMed/NCBI | |
Rosen E, Fatanmi OO, Wise SY, Rao VA and Singh VK: Gamma-tocotrienol, a radiation countermeasure, reverses proteomic changes in serum following total-body gamma irradiation in mice. Sci Rep. 12:33872022. View Article : Google Scholar : PubMed/NCBI | |
Rosen E, Fatanmi OO, Wise SY, Rao VA and Singh VK: Tocol prophylaxis for total-body irradiation: A proteomic analysis in murine model. Health Phys. 119:12–20. 2020. View Article : Google Scholar : PubMed/NCBI | |
Rithidech KN, Honikel L, Rieger R, Xie W, Fischer T and Simon SR: Protein-expression profiles in mouse blood-plasma following acute whole-body exposure to (137)Cs gamma rays. Int J Radiat Biol. 85:432–447. 2009. View Article : Google Scholar : PubMed/NCBI | |
Zutler M, Quinlan PJ and Blanc PD: Alpha-1-antitrypsin deficient man presenting with lung function decline associated with dust exposure: A case report. J Med Case Rep. 5:1542011. View Article : Google Scholar : PubMed/NCBI | |
Bolund AC, Miller MR, Sigsgaard T and Schlünssen V: The effect of organic dust exposure on long-term change in lung function: A systematic review and meta-analysis. Occup Environ Med. 74:531–542. 2017. View Article : Google Scholar : PubMed/NCBI | |
Liao SY, Lin X and Christiani DC: Occupational exposures and longitudinal lung function decline. Am J Ind Med. 58:14–20. 2015. View Article : Google Scholar : PubMed/NCBI |