{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T23:06:33Z","timestamp":1784934393707,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,5]],"date-time":"2009-02-05T00:00:00Z","timestamp":1233792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Council of Scientific and Industrial Research, Government of India","award":["Network Project (NWP 0038)"],"award-info":[{"award-number":["Network Project (NWP 0038)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Curative effect of cystatin, a natural cystein protease inhibitor, on experimental visceral leishmaniasis was associated with strong upregulation of iNOS. The transductional mechanisms underlying this cellular response was investigated in the murine macrophage cell line RAW 264.7 and in the BALB\/c mouse model of visceral leishmaniasis. Cystatin synergizes with IFN\u2010\u03b3 in inducing ERK1\/2 phosphorylation and NF\u2010\u03baB DNA\u2010binding activity. Pretreatment of cells with specific inhibitors of NF\u2010\u03baB or ERK1\/2 pathway blocked the cystatin plus IFN\u2010\u03b3\u2010inducible NF\u2010\u03baB activity and markedly reduced the expression of iNOS at both mRNA and protein levels. Silencing of mitogen\u2010 and stress\u2010activated protein kinase 1 significantly reduced cystatin\u2010mediated NF\u2010\u03baB\u2010dependent iNOS gene transcription suggesting the involvement of mitogen\u2010 and stress\u2010activated protein kinase 1 activation in ERK1\/2 signaling. DNA binding as well as silencing experiments revealed the requirement of IFN\u2010\u03b3\u2010mediated JAK\u2010STAT activation even though cystatin did not modulate this signaling cascade by itself. In the <jats:italic>in vivo<\/jats:italic> situation, key steps in the activation cascade of NF\u2010\u03baB, including nuclear translocation of NF\u2010\u03baB subunits, I\u03baB phosphorylation and I\u03baB kinase, are all remarkably enhanced in <jats:italic>Leishmania<\/jats:italic>\u2010infected mice by cystatin. Understanding the molecular mechanisms through which cystatin modulates macrophage effector responses will contribute to better define its potential for macrophage\u2010associated diseases, in general.<\/jats:p>","DOI":"10.1002\/eji.200838465","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T02:44:09Z","timestamp":1233974649000},"page":"741-751","source":"Crossref","is-referenced-by-count":19,"title":["Signaling events leading to the curative effect of cystatin on experimental visceral leishmaniasis: Involvement of ERK1\/2, NF\u2010\u03baB and JAK\/STAT pathways"],"prefix":"10.1002","volume":"39","author":[{"given":"Susanta","family":"Kar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindita","family":"Ukil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pijush K.","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,3,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.893"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2003.01206.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.6.1779"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6271"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.22.2723"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/89769"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(98)00056-X"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/hq1201.099424"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1797"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5734"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-11-1007"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(2000)30:8<2235::AID-IMMU2235>3.0.CO;2-9"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00067-5"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(98)80065-9"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.6008"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.7.3711"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4020"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.28077"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01555-06"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409885200"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.277.4.H1641"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.2011"},{"key":"e_1_2_6_24_2","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1128\/IAI.67.8.4055-4063.1999","article-title":"Activation of phosphotyrosine phosphatase activity attenuates mitogen\u2010activated protein kinase signaling and inhibits c\u2010FOS and nitric oxide synthase expression in macrophages infected with Leishmania donovani","volume":"67","author":"Nandan D.","year":"1999","journal-title":"Infect. Immun."},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.6828-6838.2002"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg139"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80222-6"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni828"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90311-9"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.9.4406"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.1995"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.3297"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112210200"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.2.1161"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/314929"},{"key":"e_1_2_6_36_2","doi-asserted-by":"crossref","first-page":"929","DOI":"10.4049\/jimmunol.151.2.929","article-title":"Role and effect of IL\u20102 in experimental visceral leishmaniasis","volume":"151","author":"Murray H. W.","year":"1993","journal-title":"J. Immunol."},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500566200"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.200838465","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.200838465","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.200838465","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T19:32:03Z","timestamp":1695929523000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.200838465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["10.1002\/eji.200838465"],"URL":"https:\/\/doi.org\/10.1002\/eji.200838465","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3]]}}}