{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:03:07Z","timestamp":1773284587198,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T00:00:00Z","timestamp":1625961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Uveitis is characterized by inflammatory lesions of intraocular structures. It is one of the important manifestations in patients with Reiter\u2019s syndrome, an inflammatory arthritis, which is caused by enteric infection with bacteria, including Salmonella typhimurium. Corticosteroids remain the most frequently used therapies against uveitis associating with inflammatory arthritis. However, the long-term administration of steroids results in many side effects, and some uveitis patients do not respond to steroid treatment. Non-steroidal treatments are needed for uveitis patients. Our previous study found that Janus kinase (JAK) 1\/2 inhibitor, ruxolitinib could suppress the expression of proinflammatory mediators in the ciliary body and iris. However, the impacts of ruxolitinib on ophthalmic features in uveitic eyes are still unknown. In this study, Salmonella typhimurium endotoxin-induced uveitis (EIU) was induced in Sprague Dawley rats by the injection of lipopolysaccharide (LPS). Compared with LPS-induced rats treated with water, ruxolitinib significantly attenuated the clinical manifestations, infiltrating cells and protein exudation in the aqueous humor, and retina\u2013choroid thickening. Amplitudes of b-wave in both scotopic and photopic electroretinogram (ERG), and the amplitude of a-wave in scotopic ERG in EIU animals were alleviated by ruxolitinib. Collectively, we propose ruxolitinib could attenuate endotoxin-induced uveitis and rescue visual functions in rats by inhibiting the JAK2-STAT3 pathway.<\/jats:p>","DOI":"10.3390\/microorganisms9071481","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:23:36Z","timestamp":1626049416000},"page":"1481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ruxolitinib Alleviates Uveitis Caused by Salmonella typhimurium Endotoxin"],"prefix":"10.3390","volume":"9","author":[{"given":"Lin","family":"Du","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda Wong Ying","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Him Kwan","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-3868","authenticated-orcid":false,"given":"Bo Man","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Molecular Biotechnology Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Na","family":"He","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun On","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi Pui","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2903-3247","authenticated-orcid":false,"given":"Wai Kit","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1521-6942(02)00104-3","article-title":"Arthritis associated with enteric infection","volume":"17","author":"Lillicrap","year":"2003","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0161-6420(86)33747-3","article-title":"The clinical diagnosis of Reiter\u2019s syndrome. Ophthalmic and nonophthalmic aspects","volume":"93","author":"Lee","year":"1986","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/bjo.80.4.332","article-title":"Causes and frequency of blindness in patients with intraocular inflammatory disease","volume":"80","author":"Rothova","year":"1996","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41433-018-0223-z","article-title":"Noninfectious uveitis in the Asia-Pacific region","volume":"33","author":"Hsu","year":"2019","journal-title":"Eye"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Qin, Y.J., Chu, K.O., Yip, Y.W., Li, W.Y., Yang, Y.P., Chan, K.P., Ren, J.L., Chan, S.O., and Pang, C.P. (2014). Green tea extract treatment alleviates ocular inflammation in a rat model of endotoxin-induced uveitis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103995"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1159\/000488472","article-title":"Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF-kappabeta Pathway in Endotoxin-Induced Uveitis","volume":"46","author":"Tang","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1167\/iovs.17-22679","article-title":"The Anti-Inflammatory Effect of Ripasudil (K-115), a Rho Kinase (ROCK) Inhibitor, on Endotoxin-Induced Uveitis in Rats","volume":"58","author":"Uchida","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1167\/iovs.10-5892","article-title":"Effect of artesunate on endotoxin-induced uveitis in rats","volume":"52","author":"Wang","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1046\/j.1440-1711.1998.00783.x","article-title":"Basic pathogenic mechanisms operating in experimental models of acute anterior uveitis","volume":"76","author":"Smith","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.exer.2019.02.021","article-title":"Growth hormone-releasing hormone receptor mediates cytokine production in ciliary and iris epithelial cells during LPS-induced ocular inflammation","volume":"181","author":"Ren","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1073\/pnas.1904532117","article-title":"Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation","volume":"117","author":"Liang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0165-5728(98)00042-3","article-title":"Effect of macrophage depletion by liposomes containing dichloromethylene-diphosphonate on endotoxin-induced uveitis","volume":"86","author":"Pouvreau","year":"1998","journal-title":"J. Neuroimmunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.toxlet.2009.08.025","article-title":"Lipopolysaccharide triggers macrophage activation of inflammatory cytokine expression, chemotaxis, phagocytosis, and oxidative ability via a toll-like receptor 4-dependent pathway: Validated by RNA interference","volume":"191","author":"Wu","year":"2009","journal-title":"Toxicol. Lett."},{"key":"ref_14","first-page":"1949","article-title":"Endotoxin-induced uveitis. Kinetics and phenotype of the inflammatory cell infiltrate and the response of the resident tissue macrophages and dendritic cells in the iris and ciliary body","volume":"36","author":"McMenamin","year":"1995","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_15","first-page":"473","article-title":"Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model","volume":"9","author":"Chu","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1016\/S0161-6420(03)00620-1","article-title":"Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter\u2019s syndrome","volume":"110","author":"Kiss","year":"2003","journal-title":"Ophthalmology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF02231693","article-title":"Acute anterior uveitis in juvenile Reiter\u2019s syndrome","volume":"15","author":"Fischel","year":"1996","journal-title":"Clin. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.2147\/OPTH.S118409","article-title":"Systemic side effects of eye drops: A pharmacokinetic perspective","volume":"10","author":"Farkouh","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41433-018-0224-y","article-title":"Infectious uveitis: An Asian perspective","volume":"33","author":"Agarwal","year":"2019","journal-title":"Eye"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/ni.3691","article-title":"Mechanisms and consequences of Jak-STAT signaling in the immune system","volume":"18","author":"Villarino","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(02)00398-0","article-title":"Signaling through the JAK\/STAT pathway, recent advances and future challenges","volume":"285","author":"Kisseleva","year":"2002","journal-title":"Gene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0092-8674(00)81166-6","article-title":"Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses","volume":"93","author":"Rodig","year":"1998","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102390","DOI":"10.1016\/j.autrev.2019.102390","article-title":"JAK inhibitors for the treatment of autoimmune and inflammatory diseases","volume":"18","author":"Jamilloux","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1093\/rheumatology\/kez002","article-title":"Clinical significance of Janus Kinase inhibitor selectivity","volume":"58","author":"Choy","year":"2019","journal-title":"Rheumatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"82","DOI":"10.12688\/f1000research.13167.1","article-title":"JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders","volume":"7","author":"Vainchenker","year":"2018","journal-title":"F1000Research"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1124\/dmd.110.033787","article-title":"Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus tyrosine kinase 1\/2 inhibitor, in humans","volume":"38","author":"Shilling","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1182\/blood-2013-12-543736","article-title":"Activity of therapeutic JAK 1\/2 blockade in graft-versus-host disease","volume":"123","author":"Spoerl","year":"2014","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1038\/leu.2015.212","article-title":"Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey","volume":"29","author":"Zeiser","year":"2015","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000267163","article-title":"Retino-choroidal changes in endotoxin-induced uveitis in the rat","volume":"24","author":"Thillaye","year":"1992","journal-title":"Ophthalmic Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6254","DOI":"10.1167\/iovs.12-9450","article-title":"Tracking retinal microgliosis in models of retinal ganglion cell damage","volume":"53","author":"Liu","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1167\/iovs.17-22436","article-title":"Quantitative Characterization of Autoimmune Uveoretinitis in an Experimental Mouse Model","volume":"58","author":"Li","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6504","DOI":"10.1167\/iovs.10-5551","article-title":"Tracking longitudinal retinal changes in experimental ocular hypertension using the cSLO and spectral domain-OCT","volume":"51","author":"Guo","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/IIO.0000000000000072","article-title":"The role of sex in uveitis and ocular inflammation","volume":"55","author":"Yeung","year":"2015","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.4049\/jimmunol.180.9.6070","article-title":"Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases","volume":"180","author":"Liu","year":"2008","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s10067-019-04875-w","article-title":"JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis","volume":"39","author":"Miserocchi","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1080\/09273948.2019.1605453","article-title":"Effect of Janus Kinase Inhibitor Treatment on Anterior Uveitis and Associated Macular Edema in an Adult Patient with Juvenile Idiopathic Arthritis","volume":"27","author":"Bauermann","year":"2019","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMoa1110557","article-title":"A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis","volume":"366","author":"Verstovsek","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.3109\/10428194.2014.963082","article-title":"Pulmonary tuberculosis reactivation following ruxolitinib treatment in a patient with primary myelofibrosis","volume":"56","author":"Chen","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1038\/leu.2014.104","article-title":"Disseminated tuberculosis associated with ruxolitinib","volume":"28","author":"Hopman","year":"2014","journal-title":"Leukemia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"bcr2014204950","DOI":"10.1136\/bcr-2014-204950","article-title":"Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy","volume":"2014","author":"Lee","year":"2014","journal-title":"BMJ Case Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1056\/NEJMc1302895","article-title":"Bilateral toxoplasmosis retinitis associated with ruxolitinib","volume":"369","author":"Goldberg","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.jaad.2017.02.049","article-title":"Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib","volume":"76","author":"Rothstein","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/ICO.0000000000000019","article-title":"Effects of topical Janus kinase inhibition on ocular surface inflammation and immunity","volume":"33","author":"Stevenson","year":"2014","journal-title":"Cornea"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"546","DOI":"10.21037\/atm-20-2972","article-title":"Ruxolitinib protects lipopolysaccharide (LPS)-induced sepsis through inhibition of nitric oxide production in mice","volume":"8","author":"Li","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1002\/eji.202048922","article-title":"JAK inhibitors: Ten years after","volume":"51","author":"Spinelli","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1167\/iovs.02-0589","article-title":"Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo","volume":"44","author":"Koizumi","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"643525","DOI":"10.1155\/2014\/643525","article-title":"Effect of the Toll-like receptor 4 antagonist eritoran on retinochoroidal inflammatory damage in a rat model of endotoxin-induced inflammation","volume":"2014","author":"Ekici","year":"2014","journal-title":"Mediat. Inflamm."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1481\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:29:00Z","timestamp":1760164140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/7\/1481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,11]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["microorganisms9071481"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9071481","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,11]]}}}