{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:37:02Z","timestamp":1789385822562,"version":"build-2803163510"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-32 is a multifaceted cytokine with a role in infections, autoimmune diseases, and cancer, and it exerts diverse functions, including aggravation of inflammation and inhibition of virus propagation. We previously identified IL-32 as a critical regulator of endothelial cell (EC) functions, and we now reveal that IL-32 also possesses angiogenic properties. The hyperproliferative ECs of human pulmonary arterial hypertension and glioblastoma multiforme exhibited a markedly increased abundance of IL-32, and, significantly, the cytokine colocalized with integrin \u03b1V\u03b23. Vascular endothelial growth factor (VEGF) receptor blockade, which resulted in EC hyperproliferation, increased IL-32 three-fold. Small interfering RNA\u2013mediated silencing of IL-32 negated the 58% proliferation of ECs that occurred within 24 h in scrambled-transfected controls. Reduction of IL-32 neither affected apoptosis (insignificant changes in Bak-1, Bcl-2, Bcl-xL, lactate dehydrogenase, annexin V, and propidium iodide) nor VEGF or TGF-\u03b2 levels, but siIL-32\u2013transfected adult and neonatal ECs produced up to 61% less NO, IL-8, and matrix metalloproteinase-9, and up to 3-fold more activin A and endostatin. In coculture-based angiogenesis assays, IL-32\u03b3 dose-dependently increased tube formation up to 3-fold; an \u03b1V\u03b23 inhibitor prevented this activity and reduced IL-32\u03b3\u2013induced IL-8 by 85%. In matrigel plugs loaded with IL-32\u03b3, VEGF, or vehicle and injected into live mice, we observed the anticipated VEGF-induced increase in neocapillarization (8-fold versus vehicle), but unexpectedly, IL-32\u03b3 was equally angiogenic. A second signal such as IFN-\u03b3 was required to render cells responsive to exogenous IL-32\u03b3; importantly, this was confirmed using a completely synthetic preparation of IL-32\u03b3. In summary, we add angiogenic properties that are mediated by integrin \u03b1V\u03b23 but VEGF-independent to the portfolio of IL-32, implicating a role for this versatile cytokine in pulmonary arterial hypertension and neoplastic diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1202802","type":"journal-article","created":{"date-parts":[[2013,12,12]],"date-time":"2013-12-12T03:26:31Z","timestamp":1386818791000},"page":"589-602","source":"Crossref","is-referenced-by-count":88,"title":["IL-32 Promotes Angiogenesis"],"prefix":"10.1093","volume":"192","author":[{"given":"Claudia A","family":"Nold-Petry","sequence":"first","affiliation":[{"name":"Ritchie Centre, Monash Institute of Medical Research, Monash University , Melbourne, Victoria 3168,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Rudloff","sequence":"additional","affiliation":[{"name":"Ritchie Centre, Monash Institute of Medical Research, Monash University , Melbourne, Victoria 3168,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Baumer","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii , Honolulu, HI 96813"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menotti","family":"Ruvo","sequence":"additional","affiliation":[{"name":"Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerce e Centro Interuniversitario di Ricerca sui Peptidi Bioattivi , 80134 Naples,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marasco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II , 80134 Naples,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Botti","sequence":"additional","affiliation":[{"name":"ArisGen SA , 1228 Plan-les-Ouates,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Farkas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Virginia Commonwealth University , Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven X","family":"Cho","sequence":"additional","affiliation":[{"name":"Ritchie Centre, Monash Institute of Medical Research, Monash University , Melbourne, Victoria 3168,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarod A","family":"Zepp","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Azam","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Dinkel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent E","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A","family":"Boisvert","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii , Honolulu, HI 96813"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlyne D","family":"Cool","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laima","family":"Taraseviciene-Stewart","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"Heinhuis","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A B","family":"Joosten","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Dinarello","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver , Aurora, CO 80045"},{"name":"Radboud University Medical Center , 6500 HB Nijmegen,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert F","family":"Voelkel","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel F","family":"Nold","sequence":"additional","affiliation":[{"name":"Ritchie Centre, Monash Institute of Medical Research, Monash University , Melbourne, Victoria 3168,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,15]]},"reference":[{"key":"2025032404083975600_r1","first-page":"131","article-title":"Interleukin-32: a cytokine and inducer of TNF\u03b1","volume":"22","author":"Kim","year":"2005","journal-title":"Immunity"},{"key":"2025032404083975600_r2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/intimm\/dxh339","article-title":"Involvement of IL-32 in activation-induced cell death in T cells","volume":"18","author":"Goda","year":"2006","journal-title":"Int. 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