{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:10:43Z","timestamp":1791421843692,"version":"4.3.3"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    , the causative agent of inhalational anthrax, enters a host through the pulmonary system before dissemination. We have previously shown that human alveolar macrophages participate in the initial innate immune response to\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    spores through cell signal-mediated cytokine release. We proposed that the lung epithelia also participate in the innate immune response to this pathogen, and we have developed a human lung slice model to study this process. Exposure of our model to\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    (Sterne) spores rapidly activated the mitogen-activated protein kinase signaling pathways ERK, p38, and JNK. In addition, an RNase protection assay showed induction of mRNA of several cytokines and chemokines. This finding was reflected at the translational level by protein peak increases of 3-, 25-, 9-, 34-, and 5-fold for interleukin-6 (IL-6), tumor necrosis factor alpha, IL-8, macrophage inflammatory protein 1\u03b1\/\u03b2, and monocyte chemoattractant protein 1, respectively, as determined by an enzyme-linked immunosorbent assay. Inhibition of individual pathways by UO126, SP600125, and SB0203580 decreased induction of chemokines and cytokines by spores, but this depended on the pathways inhibited and the cytokines and chemokines induced. Combining all three inhibitors reduced induction of all cytokines and chemokines tested to background levels. An immunohistochemistry analysis of IL-6 and IL-8 revealed that alveolar epithelial cells and macrophages and a few interstitial cells are the source of the cytokines and chemokines. Taken together, these data showed the activation of the pulmonary epithelium in response to\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    spore exposure. Thus, the lung epithelia actively participate in the innate immune response to\n                    <jats:italic>B. anthracis<\/jats:italic>\n                    infection through cell signal-mediated elaboration of cytokines and chemokines.\n                  <\/jats:p>","DOI":"10.1128\/iai.00046-07","type":"journal-article","created":{"date-parts":[[2007,5,22]],"date-time":"2007-05-22T12:39:04Z","timestamp":1179837544000},"page":"3729-3738","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Human Lung Innate Immune Response to\n                    <i>Bacillus anthracis<\/i>\n                    Spore Infection"],"prefix":"10.1128","volume":"75","author":[{"given":"Kaushik","family":"Chakrabarty","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Leland","family":"Booth","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Duggan","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy N.","family":"Nagle","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Mark","family":"Coggeshall","sequence":"additional","affiliation":[{"name":"Programs in Immunology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan P.","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Department of Medicine"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"126","volume":"82","year":"1994","unstructured":"Arnold, R., B. Humbert, H. Werchau, H. Gallati, and W. Konig. 1994. Interleukin-8, interleukin-6, and soluble tumour necrosis factor receptor type I release from a human pulmonary epithelial cell line (A549) exposed to respiratory syncytial virus. Immunology82:126-133.","journal-title":"Immunology"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.8.4156-4164.2004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5545"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00017-1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00446-06"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00357-F"},{"key":"e_1_3_2_8_2","first-page":"418","volume":"92","year":"1971","unstructured":"Dalldorf, F. G., A. F. Kaufmann, and P. S. Brachman. 1971. Woolsorters' disease. An experimental model. Arch. Pathol. Lab. Med.92:418-426.","journal-title":"Arch. Pathol. Lab. Med."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.4049\/jimmunol.160.9.4175","volume":"160","year":"1998","unstructured":"DeSilva, D. R., E. A. Jones, M. F. Favata, B. D. Jaffee, R. L. Magolda, J. M. Trzaskos, and P. A. Scherle. 1998. Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy. J. Immunol.160:4175-4181.","journal-title":"J. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2000.00067.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909093411107"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.3507"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/167.5.1239"},{"key":"e_1_3_2_14_2","first-page":"691","volume":"73","year":"1995","unstructured":"Fritz, D. L., N. K. Jaax, W. B. Lawrence, K. J. Davis, M. L. Pitt, J. W. Ezzell, and A. M. Friedlander. 1995. Pathology of experimental inhalation anthrax in the rhesus monkey. Lab. Investig.73:691-702.","journal-title":"Lab. Investig."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63697-8"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(02)02422-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02695.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01137.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12466"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5870-5872.2002"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.4.3677"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3504"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1086\/515279"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7973702"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.8.4716-4722.2004"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-6-56"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.04.013"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.3069-3072.2004"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6382-6389.2004"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(87)90336-X"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00830-1"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00275-06"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00141005"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.3.3549"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.116.5.1369"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.56.3.182"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1981.tb00015.x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000080599.43791.01"},{"key":"e_1_3_2_39_2","unstructured":"Morphometry of the human lung. 1963"},{"key":"e_1_3_2_40_2","unstructured":"Biostatistical analysis. 1996"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00046-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00046-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T19:11:38Z","timestamp":1683832298000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00046-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1128\/IAI.00046-07"],"URL":"https:\/\/doi.org\/10.1128\/iai.00046-07","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1088406.541455","asserted-by":"object"}]},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]},"assertion":[{"value":"2007-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}