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We also show that downregulation or loss of Cav\u20102 increases expression of inducible nitric oxide (NO) synthase (iNOS) and subsequent NO production in activated macrophages. Treatment with LPS and IFN\u2010\u03b3 downregulated Cav\u20102 at the protein and mRNA level. Moreover, LPS\u2010 and IFN\u2010\u03b3\u2010induced downregulation of Cav\u20102 inversely correlated with iNOS expression levels. Mechanistically, activation of NF\u2010\u03baB pathway was responsible for downregulation of Cav\u20102 by LPS and IFN\u2010\u03b3 since pharmacological inhibition of NF\u2010\u03baB activation with pyrrolidine dithiocarbamate (PDTC) prevented Cav\u20102 downregulation and iNOS activation. To test if LPS\u2010 and IFN\u2010\u03b3\u2010induced downregulation of Cav\u20102 could possibly be involved in macrophage activation, we used a combination of siRNA knockdown and genetic deletion\/knockout (KO) approaches. Remarkably, reduction of Cav\u20102 using siRNA approach resulted in enhanced STAT1 phosphorylation, iNOS expression, and increased NO production in LPS\u2010 and LPS plus IFN\u2010\u03b3\u2010stimulated macrophages. Conversely, genetic deletion of Cav\u20102 robustly enhanced IFN\u2010\u03b3\u2010stimulated iNOS expression and subsequent NO production. Overall, our data suggest that Cav\u20102 is not only regulated during macrophage activation, but it also may be an important physiological regulator of macrophage activation via preventing excessive STAT1 signaling and iNOS stimulation.<\/jats:p>","DOI":"10.1155\/mi\/9244130","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T14:05:47Z","timestamp":1779717947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of Caveolin\u20102 Is a Novel Mechanism Involved in Activation of Inducible Nitric Oxide Synthase (iNOS) in Mouse Peritoneal Macrophages"],"prefix":"10.1155","volume":"2026","author":[{"given":"Sungchan","family":"Jang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8150-1525","authenticated-orcid":false,"given":"Grzegorz","family":"Sowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1937-6448(08)01804-2"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-1222-9_3"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/809259"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00135-2"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1031672100"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi701709s"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00401.2009"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.02.089"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.07.008"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00486.2010"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01079.x"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.25335"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01279.x"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-4-23"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411702200"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808629200"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067300"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.13.16234"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1408"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55368-4"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00682.2020"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568010054526359"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2007.00329.x"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3570593"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2010.04.007"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011291200"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300140-JLR200"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1078\/S0171-9335(04)70038-2"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1401s83"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1342"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.5.1181"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3020-0"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.9.5084-5089.2000"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.12.8136-8143.2005"},{"key":"e_1_2_8_35_2","article-title":"Role 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