IL13-induced lung fibrosis in meconium aspiration
ABSTRACT
We demonstrated previously that inflammatory cy-tokines TNF, IL-1, IL-6 and IL-8 are signifi-cantly expressed in meconium-instilled lungs. Capto-pril was a strong inhibitor of meconium-induced lung injury, inflammation and apoptosis and reduces lung alveolar and airway epithelial cell damage. Presently we demonstrate that IL-13 expression in the me-conium aspiration syndrome (MAS). IL-13 was maximally expressed 8 hrs after meconium instilla-tion. It was previously described that IL-13 plays a major role in degradation of airway epithelial cells and inducing of lung fibrosis by activating collagen production that is a major point in identification of lung fibrosis. We also showed that Captopril treat-ment significantly inhibits IL-13 expression in the lungs. We believe it reduces meconium-induced lung injury and has a therapeutic effect on histological and biochemical functions of the lungs and possibly pulmonary fibrosis. Captopril treatment significantly reduced the number of neuprophils and macrophages which express IL13 and levels of other inflammatory cytokines after meconium instillation. Selective neu-tralization of IL-13 ameliorated lung injury, airway hyper responsiveness, eosinophil recruitment and mucus overproduction.
We demonstrated previously that inflammatory cy-tokines TNF, IL-1, IL-6 and IL-8 are signifi-cantly expressed in meconium-instilled lungs. Capto-pril was a strong inhibitor of meconium-induced lung injury, inflammation and apoptosis and reduces lung alveolar and airway epithelial cell damage. Presently we demonstrate that IL-13 expression in the me-conium aspiration syndrome (MAS). IL-13 was maximally expressed 8 hrs after meconium instilla-tion. It was previously described that IL-13 plays a major role in degradation of airway epithelial cells and inducing of lung fibrosis by activating collagen production that is a major point in identification of lung fibrosis. We also showed that Captopril treat-ment significantly inhibits IL-13 expression in the lungs. We believe it reduces meconium-induced lung injury and has a therapeutic effect on histological and biochemical functions of the lungs and possibly pulmonary fibrosis. Captopril treatment significantly reduced the number of neuprophils and macrophages which express IL13 and levels of other inflammatory cytokines after meconium instillation. Selective neu-tralization of IL-13 ameliorated lung injury, airway hyper responsiveness, eosinophil recruitment and mucus overproduction.
Cite this paper
nullZagariya, A. , Navale, S. , Zagariya, O. , McClain, K. and Vidyasagar, D. (2011) IL13-induced lung fibrosis in meconium aspiration. Journal of Biomedical Science and Engineering, 4, 609-619. doi: 10.4236/jbise.2011.49077.
nullZagariya, A. , Navale, S. , Zagariya, O. , McClain, K. and Vidyasagar, D. (2011) IL13-induced lung fibrosis in meconium aspiration. Journal of Biomedical Science and Engineering, 4, 609-619. doi: 10.4236/jbise.2011.49077.
References
[1] Vidyasagar, D., Uhal, B., Bhat, R., Navale, S. and Zagariya, A. (2004) The TNF, IL-1, IL-6, IL-8, IL-10 and INGg cytokine expression in meconium-instilled newborn lungs. Indian Journal of Pediatrics, 71, 195-102. [2] Wisnievsky, M., Zagariya, A., Pavuluri, N., Shrinivasan, H., Navale, S. and Vidyasagar, D. (2005) Meconium induces injury in anoxic isolated perfused rat lungs. Pediatric Pulmonology, 39, 368-373. [3] Vidyasagar, D., Lukkarinen, H., Kaapa, P. and Zagariya, A. (2005) Inflammatory responce and apoptosis in newborn lungs after meconium aspiration. Biotechnology Progress, 21, 192-197. doi:10.1021/bp0497886 [4] Zagariya, A., Bhat, R., Uhal, B., Navale, S. and Vidyasagar, D. (2005) Apoptosis of airway epithelial cells in response to meconium. Life Sciences, 76, 1849-1858. doi:10.1016/j.lfs.2004.10.033 [5] Zagariya, A., Bhat, R., Uhal, B., Navale, S., Freidine, M. and Vidyasagar, D. (2000) Cell death and lung cell histology in meconium aspirated newborn rabbit lung. European Journal of Pediatrics, 159, 819-826. doi:10.1007/s004310000581 [6] Zagariya, A., Bhat, R., Navale, S. and Vidyasagar, D. (2006) Inhibition of meconium-induced cytokine expression by Captopril. Pediatrics, 117, 1722-1727. doi:10.1542/peds.2005-0274 [7] Lukkarinen, H., Laine, J., Aho, H., Zagariya, A., Vidyasagar, D. and Kaapa, P. (2004) Angiotensin II receptor blockade inhibits pneumocyte apoptosis in experimental meconium aspiration. Pediatric Research, 55, 326-333. doi:10.1203/01.PDR.0000100901.88697.66 [8] Uhal, B.D., Wang, R., Laukka, J., Zhyang, J., Soledad-Conrad, V. and Filippatos, G. (2003) Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angiotensin system antagonists. Pharmacology & Toxicology, 92, 81-87. doi:10.1034/j.1600-0773.2003.920204.x [9] Doucet, C., Brouty-Boye, D., Pottin-Clemenceau, C., Canonica, G.W., Jasmin, C. and Azzarone, B. (1998) Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. 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BioEssays, 22, 646-656. doi:10.1002/1521-1878(200007)22:7<646::AID-BIES7>3.0.CO;2-9 [14] Wills-Karp, M., Luyimbazi, J., Xu, X., Schofield, B., Neben, T.Y., Karp, C.L. and Donaldson, D.D. (1998) Interleukin IL-13: Central mediator of allergic astma. Science, 282, 2258. doi:10.1126/science.282.5397.2258 [15] Kawakami, M., Kawakami, K. and Puri, R.K. (2002) Apoptotic pathways of cell death induced by an interleukin-13 receptor-targeted recombinant cytotoxin in head and neck cancer cells. Cancer Immunology, Immunotherapy, 50, 691-700. doi:10.1007/s00262-001-0242-6 [16] Belperio, J.A., Dy, M., Burdick, M.D., Xue, Y.Y., Li, K.J.A. and Elias, M.P. (2002) Keane Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, 27, 419. [17] Oriente, A., Fedarko, N.S., Pacocha, S.E., Hugan, S.K., Lichtenstein, L.M. and Essayan, D.M. 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The American Journal of Pathology, 161, 1283-1297. doi:10.1016/S0002-9440(10)64405-7 [21] Zuo, F., Kaminski, N., Eugui, E,, Allard, J., Yakhini, Z., Ben-Dor, A., Lollini, L., Morris D., Kim, Y. and De Lustro, B. (2002) Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proceedings of the National Academy of Sciences, 99, 6292. doi:10.1073/pnas.092134099 [22] Evanoff, H., Burdick, M.D., Moore, S.A., Kunkel, S.L. and Strieter, R.M. (1992) A sensitive ELISA foe the detection of human monocyte chemoattractant protein-1 (MCP-1). Immunological Investigations, 21, 39-49. doi:10.3109/08820139209069361 [23] Graves, P.E., Kabesch M., Halonen, C.J., Holberg, M., Baldini, C., Fritzsch, S.K., Weiland, R.P., Erickson, E. and Martinez, F.D. (2000) A cluster of seven tightly linked polymorphism in the IL-13 gene is associated with total serum IgE levels in three populations of white children. 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The Journal of Experimental Medicine, 194, 809-821. doi:10.1084/jem.194.6.809 [31] Oriente, A., Fedarko, N.S., Pacocha, S.E., Huang, S.K., Lichtenstein, L.M. and Essayan, D.M. (2000) Interleukin IL-13 modulated collagen homeostasis in human skin and keloid fibroblasts. Journal of Pharmacology and Experimental Therapeutics, 292, 988-994. [32] Kunkel, S.L., Lukacs, N.W., Strieter, R.M. and Chensue, S.W. (1996) Th1 and Th2 responces regulate experimental lung granuloma development. Sarcoidosis, Vasculitis and Diffuse Lung Diseases, 160, 481-490. [33] McKenzie, A.N., Culpepper, J.A., de Malefut, W., Briere, F., Pummonen, J., Aversa, G., Sato, A., Dana, W., Cocks, B.G. and Menon, S. (1993) Interleukin IL-13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proceedings of the National Academy of Sciences, 90, 3735. doi:10.1073/pnas.90.8.3735 [34] Burd, P.R., Thompson, W.C., Max, E.E. and Mills, F.C. (1995) Activated mast cells produce interleukin IL-13. 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(2001) Cytotoxins directed at interleukin-4 receptors as therapy for brain tumors. Methods in Molecular Biology, 166, 155-176.
[1] Vidyasagar, D., Uhal, B., Bhat, R., Navale, S. and Zagariya, A. (2004) The TNF, IL-1, IL-6, IL-8, IL-10 and INGg cytokine expression in meconium-instilled newborn lungs. Indian Journal of Pediatrics, 71, 195-102. [2] Wisnievsky, M., Zagariya, A., Pavuluri, N., Shrinivasan, H., Navale, S. and Vidyasagar, D. (2005) Meconium induces injury in anoxic isolated perfused rat lungs. Pediatric Pulmonology, 39, 368-373. [3] Vidyasagar, D., Lukkarinen, H., Kaapa, P. and Zagariya, A. (2005) Inflammatory responce and apoptosis in newborn lungs after meconium aspiration. Biotechnology Progress, 21, 192-197. doi:10.1021/bp0497886 [4] Zagariya, A., Bhat, R., Uhal, B., Navale, S. and Vidyasagar, D. (2005) Apoptosis of airway epithelial cells in response to meconium. Life Sciences, 76, 1849-1858. doi:10.1016/j.lfs.2004.10.033 [5] Zagariya, A., Bhat, R., Uhal, B., Navale, S., Freidine, M. and Vidyasagar, D. (2000) Cell death and lung cell histology in meconium aspirated newborn rabbit lung. European Journal of Pediatrics, 159, 819-826. doi:10.1007/s004310000581 [6] Zagariya, A., Bhat, R., Navale, S. and Vidyasagar, D. (2006) Inhibition of meconium-induced cytokine expression by Captopril. Pediatrics, 117, 1722-1727. doi:10.1542/peds.2005-0274 [7] Lukkarinen, H., Laine, J., Aho, H., Zagariya, A., Vidyasagar, D. and Kaapa, P. (2004) Angiotensin II receptor blockade inhibits pneumocyte apoptosis in experimental meconium aspiration. Pediatric Research, 55, 326-333. doi:10.1203/01.PDR.0000100901.88697.66 [8] Uhal, B.D., Wang, R., Laukka, J., Zhyang, J., Soledad-Conrad, V. and Filippatos, G. (2003) Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angiotensin system antagonists. Pharmacology & Toxicology, 92, 81-87. doi:10.1034/j.1600-0773.2003.920204.x [9] Doucet, C., Brouty-Boye, D., Pottin-Clemenceau, C., Canonica, G.W., Jasmin, C. and Azzarone, B. (1998) Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. Journal of Clinical Investigation, 101, 2129-2139. doi:10.1172/JCI741 [10] Murata, T., Orobi, N.I., Debinski, W. and Puri, R.K. (1997) Structure of IL-13 receptor: Analysis of subunit composition in cancer and immune cells. Biochemical and Biophysical Research Communications, 238, 90-94. doi:10.1006/bbrc.1997.7248 [11] Toru, H., Pawankar, R., Ra, C., Yata, J. and Nakahata, T. (1998) Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking: enhanced IL-13 production by IL-4 primed human mast cells. Journal of Allergy and Clinical Immunology, 102, 491-502. doi:10.1016/S0091-6749(98)70140-X [12] Murata, T., Hussain, S.R., Mohri, H. and Puri, R.K. (1998) Two different receptor chains are expressed in normal human skin fibroblasts, and IL-4 and IL-13 mediate signal transduction through a common pathway. International Immunology, 10, 1103-1110. doi:10.1093/intimm/10.8.1103 [13] Brombacher, F. (2000) The role of interleukin 13 in infectious disease and allergy. BioEssays, 22, 646-656. doi:10.1002/1521-1878(200007)22:7<646::AID-BIES7>3.0.CO;2-9 [14] Wills-Karp, M., Luyimbazi, J., Xu, X., Schofield, B., Neben, T.Y., Karp, C.L. and Donaldson, D.D. (1998) Interleukin IL-13: Central mediator of allergic astma. Science, 282, 2258. doi:10.1126/science.282.5397.2258 [15] Kawakami, M., Kawakami, K. and Puri, R.K. (2002) Apoptotic pathways of cell death induced by an interleukin-13 receptor-targeted recombinant cytotoxin in head and neck cancer cells. Cancer Immunology, Immunotherapy, 50, 691-700. doi:10.1007/s00262-001-0242-6 [16] Belperio, J.A., Dy, M., Burdick, M.D., Xue, Y.Y., Li, K.J.A. and Elias, M.P. (2002) Keane Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, 27, 419. [17] Oriente, A., Fedarko, N.S., Pacocha, S.E., Hugan, S.K., Lichtenstein, L.M. and Essayan, D.M. (2000) Interleukin 13 modulates collagen homeostasis in human skin and keloid fibroblasts. Journal of Pharmacology and Experimental Therapeutics, 292, 988-994. [18] Chiaramonte, M.G., Donaldson, D.D., Cheever, A.W. and Wynn, T.A. (1999) An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. Journal of Clinical Investigation, 104, 777. doi:10.1172/JCI7325 [19] Chiaramonte, M.G., Donaldson, D.D., Cheever, A.W. and Wynn, T.A. (1999) An IL-13 inhibitor blocks the developmnt of hepatic fibrosis during a T-helper type 2-dominated inflammatory responce. Journal of Clinical Investigation, 104, 777-785. doi:10.1172/JCI7325 [20] Jakubzik, C., Kunkel, S.L., Joshi, B., Puri, R. and Hogaboam, C. (2002) Interleukin-13 fusion cytotoxin arrests Schistosoma mansoni Egg-induced pulmonary granuloma formation in mice. The American Journal of Pathology, 161, 1283-1297. doi:10.1016/S0002-9440(10)64405-7 [21] Zuo, F., Kaminski, N., Eugui, E,, Allard, J., Yakhini, Z., Ben-Dor, A., Lollini, L., Morris D., Kim, Y. and De Lustro, B. (2002) Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proceedings of the National Academy of Sciences, 99, 6292. doi:10.1073/pnas.092134099 [22] Evanoff, H., Burdick, M.D., Moore, S.A., Kunkel, S.L. and Strieter, R.M. (1992) A sensitive ELISA foe the detection of human monocyte chemoattractant protein-1 (MCP-1). Immunological Investigations, 21, 39-49. doi:10.3109/08820139209069361 [23] Graves, P.E., Kabesch M., Halonen, C.J., Holberg, M., Baldini, C., Fritzsch, S.K., Weiland, R.P., Erickson, E. and Martinez, F.D. (2000) A cluster of seven tightly linked polymorphism in the IL-13 gene is associated with total serum IgE levels in three populations of white children. The Journal of Allergy and Clinical Immunology, 105, 506-513. doi:10.1067/mai.2000.104940 [24] Uhal, B.D., Gidea, C., Bargout, R., Bifero, A., Ibarra-Sunga, O., Papp, M., Flynn, K. and Filippatos, G. (1998) Captopril inhibits apoptosis in human lung epithelial cells: A potential antifibrotic mechanism. American Journal of Physiology, 275, L1013-L1017. [25] Zheng, T., Zhu, Z., Wang, Z., Homer, R.J., Ma, B., Riese, R.J., Chapman, H.A., Shapiro, S.D. and Elias, J.A. (2000) Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. Journal of Clinical Investigation, 106, 1081-1093. doi:10.1172/JCI10458 [26] Gordon, S. (2003) Alternative activation of macrophages. Nature Reviews Immunology, 3, 23. doi:10.1038/nri978 [27] Carre, P.C., Mortenson, R.L., King, T.E., Noble, P.W., Sable, C.L. and Riches, D.W. (1991) Increased expression of the interleukin-8 gene by alveolar macrophages in idiopatic pulmonary fibrosis. Journal of Clinical Investigation, 88, 1802. doi:10.1172/JCI115501 [28] Matrinet, Y., Rom, W.N., Grotendorst, G.R., Martin, R.G. and Crystal, R.G. (1987) Exagerated spontaneous release of plateled-derived growth factor by alveolar macrophages from patients with idiopatic pulmonary fibrosis. The New England Journal of Medicine, 317, 202. doi:10.1056/NEJM198707233170404 [29] Smith, R.E., Strieter, R.M., Zhang, K., Phan, S.H., Standiford, T.J., Lukacs, N.W. and Kunkel, S.L. (1995) A role for C-C chemokines in fibrotic lung disease. Journal of Leukocyte Biology, 57, 782. [30] Lee, C.G., Homer, R.J., Zhu, Z., Lanone, S., Wang, X., Koteliansky, V., Shipley, J.M., Gotwals, P., Noble, P., Chen, Q., Senior, R.M. and Elias, J.A. (2001) Interleukin IL-13 induces tissue fibrosis by selectively stimulating and activating transforming factor beta(1). The Journal of Experimental Medicine, 194, 809-821. doi:10.1084/jem.194.6.809 [31] Oriente, A., Fedarko, N.S., Pacocha, S.E., Huang, S.K., Lichtenstein, L.M. and Essayan, D.M. (2000) Interleukin IL-13 modulated collagen homeostasis in human skin and keloid fibroblasts. Journal of Pharmacology and Experimental Therapeutics, 292, 988-994. [32] Kunkel, S.L., Lukacs, N.W., Strieter, R.M. and Chensue, S.W. (1996) Th1 and Th2 responces regulate experimental lung granuloma development. Sarcoidosis, Vasculitis and Diffuse Lung Diseases, 160, 481-490. [33] McKenzie, A.N., Culpepper, J.A., de Malefut, W., Briere, F., Pummonen, J., Aversa, G., Sato, A., Dana, W., Cocks, B.G. and Menon, S. (1993) Interleukin IL-13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proceedings of the National Academy of Sciences, 90, 3735. doi:10.1073/pnas.90.8.3735 [34] Burd, P.R., Thompson, W.C., Max, E.E. and Mills, F.C. (1995) Activated mast cells produce interleukin IL-13. The Journal of Experimental Medicine, 181, 1373. doi:10.1084/jem.181.4.1373 [35] Hancock, A., Armstrong, L., Gama, R., Millar, A. (1998) Production of interleukin IL-13 by alveolar macrophages from normal and fibrotic lungs. American Journal of Respiratory Cell and Molecular Biology, 18, 60. [36] Hancock, A., Armstrong, L., Gama, R. and Millar, A. (1998) Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. American Journal of Respiratory Cell and Molecular Biology, 18, 60. [37] Fine, A., Janssen-Heininger, Y., Soultanakis, R.P., Swisher, S.G. and Uhal, B.D. (2000) Apoptosis in lung pathophysiology. American Journal of Physiology, 279, L423-L427. [38] Soengas, M.S., Alarcon, R.M., Yoshida, H., Giaccia, A.J., Hakem, R., Mak, T.W. and Lowe, S.W. (1999) Apaf-1 and caspase 3 in p53-dependent apoptosis and tumor inhibition. Science, 284, 156-159. doi:10.1126/science.284.5411.156 [39] Puri, R.K. (2001) Cytotoxins directed at interleukin-4 receptors as therapy for brain tumors. Methods in Molecular Biology, 166, 155-176.