{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:11:34Z","timestamp":1789985494155,"version":"4.0.1"},"reference-count":40,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:p>Neither Pseudomonas aeruginosa nor flagellin affected cytosolic Ca<jats:sup>2+<\/jats:sup>concentration ([Ca]<jats:sub>i<\/jats:sub>) in airway epithelial cell lines JME and Calu-3, but bacteria or flagellin activated NF-\u03baB, IL-8 promoter, and IL-8 secretion. ATP (purinergic agonist) and thapsigargin (blocks Ca<jats:sup>2+<\/jats:sup>pump, releases endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>, and triggers Ca<jats:sup>2+<\/jats:sup>entry through plasma membrane channels) both increased [Ca]<jats:sub>i<\/jats:sub>but hardly stimulated NF-\u03baB and IL-8. ATP and thapsigargin elicited larger, synergistic activations of NF-\u03baB and IL-8 secretion when combined with flagellin. BAPTA-AM (to buffer [Ca]<jats:sub>i<\/jats:sub>) or Ca<jats:sup>2+<\/jats:sup>-free solution reduced increases in [Ca]<jats:sub>i<\/jats:sub>due to ATP or thapsigargin and also reduced NF-\u03baB activation and IL-8 secretion triggered by flagellin, ATP, thapsigargin, ATP + flagellin, and thapsigargin + flagellin. IL-8 promoter analysis showed that AP-1 and CCAAT\/enhancer-binding protein (C\/EBP)\u03b2\/nuclear factor for IL-6 (NF-IL6) sites were important for IL-8 expression, and the NF-\u03baB-binding site was critical for activation by all agonists and for activation by [Ca]<jats:sub>i<\/jats:sub>. Thus increased [Ca]<jats:sub>i<\/jats:sub>was not required for P. aeruginosa- or flagellin-activated NF-\u03baB and IL-8 expression and secretion, and increased [Ca]<jats:sub>i<\/jats:sub>was only weakly stimulatory during activation by ATP or thapsigargin. However, ATP- or thapsigargin-induced increases in [Ca]<jats:sub>i<\/jats:sub>synergized with flagellin or P. aeruginosa, and buffering or reducing [Ca]<jats:sub>i<\/jats:sub>reduced these responses. Thus [Ca]<jats:sub>i<\/jats:sub>plays an important regulatory role in P. aeruginosa- or flagellin-activated innate immune responses in airway epithelia. Dose-dependent responses indicated that flagellin-ATP synergism occurred most prominently at ATP concentrations ([ATP]) &gt; 10 \u03bcM and [flagellin] &gt;10<jats:sup>\u22128<\/jats:sup>g\/ml and during steady increases rather than oscillations in [Ca]<jats:sub>i<\/jats:sub>.<\/jats:p>","DOI":"10.1152\/ajplung.00042.2006","type":"journal-article","created":{"date-parts":[[2006,9,9]],"date-time":"2006-09-09T01:00:23Z","timestamp":1157763623000},"page":"L353-L364","source":"Crossref","is-referenced-by-count":36,"title":["Role of Ca<sup>2+<\/sup>in responses of airway epithelia to<i>Pseudomonas aeruginosa<\/i>, flagellin, ATP, and thapsigargin"],"prefix":"10.1152","volume":"292","author":[{"given":"Zhu","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Bettega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susheela","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry R.","family":"Buchholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry E.","family":"Machen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0260OC"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, Imagawa K, Kikuchi M, Mukaida N, Matsushima K.Mechanisms involved inHelicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45.Infect Immun65: 3218\u20133224, 1997.","DOI":"10.1128\/IAI.65.8.3218-3224.1997"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00747.x"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1038\/nature02196"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2865"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/386855a0"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401858"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.5.C1284"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.4.1438"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Grynkiewicz G, Poenie M, Tsien RY.A new generation of Ca2+indicators with greatly improved fluorescence properties.J Biol Chem260: 3440\u20133450, 1985.","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.12.6820"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Hoffmann E, Dittrich-Breiholz O, Holtmann H, Kracht M.Multiple control of interleukin-8 gene expression.J Leukoc Biol72: 847\u2013855, 2002.","DOI":"10.1189\/jlb.72.5.847"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2003.00342.x"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6399-6408.2002"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1990.259.6.L496"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00066.2004"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1999.276.6.L891"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.3.L493"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4454fje"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.274.3.L450"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0441OC"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161290898"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(90)92062-I"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007532200"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.117.1.53"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.903"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007703200"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.257.4.C722"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410617200"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410618200"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102061200"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.269.5.L561"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1038\/ni1011"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00166.2005"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.256.5.C1054"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.256.5.C1033"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.4.2396"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7151-7160.2005"},{"key":"R40","unstructured":"Zhang Z, Louboutin J, Weiner DJ, Wilson JM.Role of TLR5-P38 MAPK signaling in response toPseudomonas aeruginosa(Abstract).Pediatr Pulmonol Suppl28: 232, 2005."}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00042.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T20:10:09Z","timestamp":1683576609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00042.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1]]}},"alternative-id":["10.1152\/ajplung.00042.2006"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00042.2006","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,1]]}}}