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IFN\u03b3, a key cytokine in TB, usually inhibits MMP\u20109 secretion. Addition of IFN\u03b3 to conditioned media from\n                    <jats:italic>M. tb<\/jats:italic>\n                    \u2010infected monocytes (CoMTB) resulted in a 7\u2010fold increase in MMP\u20109 activity detected by gelatin zymography (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). In contrast, tissue inhibitor of metalloproteinase (TIMP)\u20101 and \u20102 secretion, measured by ELISA, was suppressed. Dexamethasone abolished the synergistic increase in MMP\u20109 activity. Interleukin (IL)\u20101\u03b2 in CoMTB is a critical mediator of synergy with IFN\u03b3, and IL\u20101\u03b2 alone synergizes with IFN\u03b3 to increase MMP\u20109 secretion from 51 \u00b1 31 to 762 \u00b1 136 U. IL\u20101\u03b2 activity is dependent on p38 mitogen\u2010activated protein (MAPK) kinase, which was found to be phosphorylated in tissue specimens from patients with CNS\u2010TB. Extracellular signal regulated kinase (Erk) and p38 MAPK activation did not affect IFN\u03b3 signaling pathways. Inhibition of janusactivated kinase (JAK)\u20102 by 50 \u03bcM AG540 decreased MMP\u20109 secretion to 124 \u00b1 11.1 from 651 \u00b1 229 U of activity (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). However, signal transducer and activator of transcription (STAT)\u20103 but not STAT\u20101 phosphorylation was synergistically up\u2010regulated by IFN\u03b3 and CoMTB. In summary, synergy between IL\u20101\u03b2 and STAT\u20103 dependent IFN\u03b3 signaling is key in control of up\u2010regulation of MMP\u20109 activity in CNS\u2010TB and may be a significant mechanism of brain tissue destruction.\u2014Harris, J. E., Fernandez\u2010Vilaseca, M., Elkington, P. T. G., Horncastle, D. E., Graeber, M. B., and Friedland, J. S. IFN\u03b1 synergizes with IL\u20101\u03b2 to upregulate MMP\u20109 secretion in a cellular model of central nervous system tuberculosis.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    21, 356\u2013365 (2007)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-6925com","type":"journal-article","created":{"date-parts":[[2006,12,12]],"date-time":"2006-12-12T05:41:47Z","timestamp":1165902107000},"page":"356-365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["IFN' synergizes with IL\u20101\u03b1 to up\u2010regulate MMP\u20109 secretion in a cellular model of central nervous system tuberculosis"],"prefix":"10.1096","volume":"21","author":[{"given":"James E.","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Immunity Imperial College Hammersmith Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Fernandez\u2010Vilaseca","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunity Imperial College Hammersmith Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T. G.","family":"Elkington","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunity Imperial College Hammersmith Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna E.","family":"Horncastle","sequence":"additional","affiliation":[{"name":"Department of Histopathology Imperial College Hammersmith Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel B.","family":"Graeber","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Imperial College Charing Cross Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon S.","family":"Friedland","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunity Imperial College Hammersmith Campus  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,12,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(05)70019-3"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0033-8389(22)00616-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1081\/NCN-200027451"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.3.289"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5333"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.051979"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/200420155"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10270"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1054\/jocn.1999.0212"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-19-07724.2001"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00303-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4223"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/417029a"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199801)22:1<53::AID-GLIA5>3.0.CO;2-9"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.8.3.255"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490420307"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.10.007"},{"key":"e_1_2_6_19_1","first-page":"209","article-title":"Central nervous system tuberculosis with and without HIV infection\u2014 clinical, neuroimaging, and neuropathological study","volume":"40","author":"Kurisaki H.","year":"2000","journal-title":"Rinsho Shinkeigaku"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02682.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2005.00711.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4367"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/21.4.924"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4367"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.5.1104"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1381.1999.99242.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.579"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071545"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406413200"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.3.391"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122075799"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/10799900152434367"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203306"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/10799900152434367"},{"key":"e_1_2_6_35_1","first-page":"808","article-title":"Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon\u2010alpha administration","volume":"58","author":"Dinney C. 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