{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:35:42Z","timestamp":1783748142602,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY023226"],"award-info":[{"award-number":["R01EY023226"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY004068"],"award-info":[{"award-number":["P30EY004068"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted"],"award-info":[{"award-number":["Unrestricted"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Previous work examining the therapeutic efficacy of adjunct thymosin beta 4 (T\u03b24) to ciprofloxacin for ocular infectious disease has revealed markedly reduced inflammation (inflammatory mediators and innate immune cells) with increased activation of wound healing pathways. Understanding the therapeutic mechanisms of action have further revealed a synergistic effect with ciprofloxacin to enhance bacterial killing along with a regulatory influence over macrophage effector cell function. As a natural extension of the aforementioned work, the current study uses an experimental model of P. aeruginosa-induced keratitis to examine the influence of T\u03b24 regarding polymorphonuclear leukocyte (PMN\/neutrophil) cellular function, contributing to improved disease response. Flow cytometry was utilized to phenotypically profile infiltrating PMNs after infection. The generation of reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and PMN apoptosis were investigated to assess the functional activities of PMNs in response to T\u03b24 therapy. In vitro work using peritoneal-derived PMNs was similarly carried out to verify and extend our in vivo findings. The results indicate that the numbers of infiltrated PMNs into infected corneas were significantly reduced with adjunctive T\u03b24 treatment. This was paired with the downregulated expression of proinflammatory markers on these cells, as well. Data generated from PMN functional studies suggested that the corneas of adjunctive T\u03b24 treated B6 mice exhibit a well-regulated production of ROS, NETs, and limited PMN apoptosis. In addition to confirming the in vivo results, the in vitro findings also demonstrated that neutrophil elastase (NE) was unnecessary for NETosis. Collectively, these data provide additional evidence that adjunctive T\u03b24 + ciprofloxacin treatment is a promising option for bacterial keratitis that addresses both the infectious pathogen and cellular-mediated immune response, as revealed by the current study.<\/jats:p>","DOI":"10.3390\/cells10123579","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:41:55Z","timestamp":1639946515000},"page":"3579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Adjunctive Thymosin Beta-4 Treatment Influences PMN Effector Cell Function during Pseudomonas aeruginosa-Induced Corneal Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"Yuxin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Carion","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Shukkur","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4805-7327","authenticated-orcid":false,"given":"Gabriel","family":"Sosne","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-1170","authenticated-orcid":false,"given":"Elizabeth A.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/eye.2011.288","article-title":"Contact lens-related microbial keratitis: How have epidemiology and genetics helped us with pathogenesis and prophylaxis","volume":"26","author":"Stapleton","year":"2012","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1099\/jmm.0.001110","article-title":"Pseudomonas aeruginosa and microbial keratitis","volume":"69","author":"Hilliam","year":"2020","journal-title":"J. Med. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1167\/iovs.11-7840","article-title":"Pseudomonas aeruginosa keratitis: Outcomes and response to corticosteroid treatment","volume":"53","author":"Sy","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"P1","DOI":"10.1016\/j.ophtha.2018.10.018","article-title":"Bacterial Keratitis Preferred Practice Pattern(R)","volume":"126","author":"Lin","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/ICO.0b013e318156caf2","article-title":"Risk factors and causative organisms in microbial keratitis","volume":"27","author":"Green","year":"2008","journal-title":"Cornea"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1444-0938.2002.tb03082.x","article-title":"The pathogenesis of bacterial keratitis: Studies with Pseudomonas aeruginosa","volume":"85","author":"Fleiszig","year":"2002","journal-title":"Clin. Exp. Optom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fcimb.2017.00039","article-title":"Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence","volume":"7","author":"Moradali","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/OPX.0b013e3180439c3e","article-title":"Pseudomonas aeruginosa infection and inflammation during contact lens wear: A review","volume":"84","author":"Willcox","year":"2007","journal-title":"Optom. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2003.10.002","article-title":"Corneal response to Pseudomonas aeruginosa infection","volume":"23","author":"Hazlett","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.micinf.2003.09.014","article-title":"Phagocytosis by neutrophils","volume":"5","author":"Lee","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Juan, C.A., P\u00e9rez de la Lastra, J.M., Plou, F.J., and P\u00e9rez-Lebe\u00f1a, E. (2021). The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094642"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105066","DOI":"10.1016\/j.micpath.2021.105066","article-title":"Multi-facets of neutrophil extracellular trap in infectious diseases: Moving beyond immunity","volume":"158","author":"Tabrizi","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.201006052","article-title":"Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps","volume":"191","author":"Papayannopoulos","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Geddes-McAlister, J., Kugadas, A., and Gadjeva, M. (2019). Tasked with a Challenging Objective: Why Do Neutrophils Fail to Battle Pseudomonas aeruginosa Biofilms. Pathogens, 8.","DOI":"10.3390\/pathogens8040283"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.chom.2019.02.007","article-title":"Neutrophil Extracellular Traps Confine Pseudomonas aeruginosa Ocular Biofilms and Restrict Brain Invasion","volume":"25","author":"Thanabalasuriar","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/sciimmunol.aar6676","article-title":"Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps","volume":"3","author":"Chen","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/imr.12453","article-title":"Clearance of apoptotic neutrophils and resolution of inflammation","volume":"273","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.jcjo.2012.09.001","article-title":"Fluoroquinolones or fortified antibiotics for treating bacterial keratitis: Systematic review and meta-analysis of comparative studies","volume":"47","author":"Hanet","year":"2012","journal-title":"Can. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1136\/bjophthalmol-2013-304660","article-title":"Topical antibiotics for the management of bacterial keratitis: An evidence-based review of high quality randomised controlled trials","volume":"98","author":"McDonald","year":"2014","journal-title":"Br. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1001\/jamaophthalmol.2015.3888","article-title":"Antibiotic Resistance Among Ocular Pathogens in the United States: Five-Year Results From the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) Surveillance Study","volume":"133","author":"Asbell","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2147\/OPTO.S189115","article-title":"Antibiotic resistance among ocular pathogens: Current trends from the ARMOR surveillance study (2009\u20132016)","volume":"11","author":"Thomas","year":"2019","journal-title":"Clin. Optom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1517\/14712598.2012.634793","article-title":"Thymosin beta4: A multi-functional regenerative peptide. Basic properties and clinical applications","volume":"12","author":"Goldstein","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1167\/iovs.15-16890","article-title":"Primary Mechanisms of Thymosin beta4 Repair Activity in Dry Eye Disorders and Other Tissue Injuries","volume":"56","author":"Sosne","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1006\/exer.2001.1125","article-title":"Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury","volume":"74","author":"Sosne","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1006\/exer.2000.0985","article-title":"Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo","volume":"72","author":"Sosne","year":"2001","journal-title":"Exp. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/jcp.20650","article-title":"Thymosin beta4 promotes matrix metalloproteinase expression during wound repair","volume":"208","author":"Philp","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1136\/bjo.2007.136747","article-title":"Thymosin beta-4 upregulates anti-oxidative enzymes and protects human cornea epithelial cells against oxidative damage","volume":"92","author":"Ho","year":"2008","journal-title":"Br. J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.exer.2006.02.001","article-title":"Thymosin beta4 inhibits benzalkonium chloride-mediated apoptosis in corneal and conjunctival epithelial cells in vitro","volume":"83","author":"Sosne","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Carion, T.W., Ebrahim, A.S., Kracht, D., Agrawal, A., Strand, E., Kaddurah, O., McWhirter, C.R., Sosne, G., and Berger, E.A. (2018). Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas aeruginosa-Induced Keratitis. Cells, 7.","DOI":"10.3390\/cells7100145"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/wound.2013.0485","article-title":"Extracellular Matrix Reorganization during Wound Healing and Its Impact on Abnormal Scarring","volume":"4","author":"Xue","year":"2015","journal-title":"Adv. Wound Care"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Carion, T.W., Ebrahim, A.S., Alluri, S., Ebrahim, T., Parker, T., Burns, J., Sosne, G., and Berger, E.A. (2020). Antimicrobial Effects of Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy in Pseudomonas aeruginosa Induced Keratitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186840"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Y., Carion, T.W., Ebrahim, A.S., Sosne, G., and Berger, E.A. (2021). Adjunctive Thymosin Beta-4 Treatment Influences MPhi Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011016"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6576","DOI":"10.4049\/jimmunol.164.12.6576","article-title":"Prolonged elevation of IL-1 in Pseudomonas aeruginosa ocular infection regulates macrophage-inflammatory protein-2 production, polymorphonuclear neutrophil persistence, and corneal perforation","volume":"164","author":"Rudner","year":"2000","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.4049\/jimmunol.178.2.1105","article-title":"Vasoactive intestinal peptide balances pro- and anti-inflammatory cytokines in the Pseudomonas aeruginosa-infected cornea and protects against corneal perforation","volume":"178","author":"Szliter","year":"2007","journal-title":"J. Immunol."},{"key":"ref_36","first-page":"20","article-title":"Isolation of mouse neutrophils","volume":"3","author":"Luo","year":"2001","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1167\/iovs.16-19134","article-title":"Inactivation of the miR-183\/96\/182 Cluster Decreases the Severity of Pseudomonas aeruginosa-Induced Keratitis","volume":"57","author":"Muraleedharan","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Berger, E.A., McClellan, S.A., Vistisen, K.S., and Hazlett, L.D. (2013). HIF-1alpha is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003457"},{"key":"ref_39","first-page":"5026","article-title":"Immunoregulatory role of 15-lipoxygenase in the pathogenesis of bacterial keratitis","volume":"32","author":"Carion","year":"2018","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1016\/j.ajpath.2018.08.010","article-title":"A Contrast in Pathogenic Responses between C57BL\/6J and BALB\/cJ Mice Using a Model of Retinal Injury","volume":"188","author":"Shi","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1111\/j.1471-4159.2009.06294.x","article-title":"Increased lipid peroxidation in Down\u2019s syndrome mouse models","volume":"110","author":"Ishihara","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2011.09.030","article-title":"Measuring reactive oxygen and nitrogen species with fluorescent probes: Challenges and limitations","volume":"52","author":"Kalyanaraman","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4350965","DOI":"10.1155\/2016\/4350965","article-title":"ROS and ROS-Mediated Cellular Signaling","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10421","DOI":"10.1038\/s41598-017-09636-w","article-title":"ROS-induced Oxidative Injury involved in Pathogenesis of Fungal Keratitis via p38 MAPK Activation","volume":"7","author":"Hua","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1089\/ars.2012.4886","article-title":"Methods for detection of mitochondrial and cellular reactive oxygen species","volume":"20","author":"Dikalov","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-94-007-7920-4_5","article-title":"Determination of HEL (Hexanoyl-lysine adduct): A novel biomarker for omega-6 PUFA oxidation","volume":"77","author":"Sakai","year":"2014","journal-title":"Subcell. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5268","DOI":"10.4049\/jimmunol.170.10.5268","article-title":"Selective roles for Toll-like receptor (TLR)2 and TLR4 in the regulation of neutrophil activation and life span","volume":"170","author":"Sabroe","year":"2003","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1167\/iovs.03-1002","article-title":"Thymosin-beta4 inhibits corneal epithelial cell apoptosis after ethanol exposure in vitro","volume":"45","author":"Sosne","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10247","DOI":"10.1038\/s41598-021-89818-9","article-title":"An intact complement system dampens cornea inflammation during acute primary HSV-1 infection","volume":"11","author":"Filiberti","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_50","first-page":"1815","article-title":"Thymosin beta4 inhibits TNF-alpha-induced NF-kappaB activation, IL-8 expression, and the sensitizing effects by its partners PINCH-1 and ILK","volume":"25","author":"Qiu","year":"2011","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_51","first-page":"877","article-title":"Thymosin beta 4 ophthalmic solution for dry eye: A randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model","volume":"9","author":"Sosne","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"23603","DOI":"10.1074\/jbc.M701120200","article-title":"The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31)","volume":"282","author":"Sachs","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1182\/blood-2010-11-321489","article-title":"CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin","volume":"118","author":"Doyle","year":"2011","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ebaid, H., Abdel-Salam, B., Hassan, I., Al-Tamimi, J., Metwalli, A., Rady, A., and Alhazza, I.M. (2020). Diabetes-Mediated Toxicity Resulted in the Expression of CD80 and CD86 on Neutrophils after Delayed Wound Healing in Male Rats. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/3592425"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/sj.cdd.4400680","article-title":"Molecular characterization of the surface of apoptotic neutrophils: Implications for functional downregulation and recognition by phagocytes","volume":"7","author":"Hart","year":"2000","journal-title":"Cell Death Differ."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8239258","DOI":"10.1155\/2016\/8239258","article-title":"Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance","volume":"2016","author":"Sugimoto","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.3389\/fimmu.2020.01259","article-title":"Multiple Roles for Chemokines in Neutrophil Biology","volume":"11","author":"Capucetti","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1161\/STROKEAHA.113.002470","article-title":"N2 neutrophils, novel players in brain inflammation after stroke: Modulation by the PPARgamma agonist rosiglitazone","volume":"44","author":"Cuartero","year":"2013","journal-title":"Stroke"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/cvr\/cvw024","article-title":"Temporal neutrophil polarization following myocardial infarction","volume":"110","author":"Ma","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2014.05.001","article-title":"Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye","volume":"125","author":"Zheng","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nrneph.2016.71","article-title":"The role of neutrophils and NETosis in autoimmune and renal diseases","volume":"12","author":"Gupta","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/jth.13239","article-title":"Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis","volume":"14","author":"Martinod","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yuan, J., Shen, Y., Yang, X., Xie, Y., Lin, X., Zeng, W., Zhao, Y., Tian, M., and Zha, Y. (2017). Thymosin beta4 alleviates renal fibrosis and tubular cell apoptosis through TGF-beta pathway inhibition in UUO rat models. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0708-1"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1159\/000363005","article-title":"Depletion of thymosin beta4 promotes the proliferation, migration, and activation of human hepatic stellate cells","volume":"34","author":"Xiao","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wei, C., Kumar, S., Kim, I.K., and Gupta, S. (2012). Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti-oxidative enzymes and anti-apoptotic genes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042586"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3109\/10520290903116884","article-title":"Exogenous thymosin beta4 prevents apoptosis in human intervertebral annulus cells in vitro","volume":"84","author":"Tapp","year":"2009","journal-title":"Biotech. Histochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1167\/iovs.08-1906","article-title":"Substance P delays apoptosis, enhancing keratitis after Pseudomonas aeruginosa infection","volume":"49","author":"Zhou","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Vemuganti, G.K., Reddy, K., Iftekhar, G., Garg, P., and Sharma, S. (2004). Keratocyte loss in corneal infection through apoptosis: A histologic study of 59 cases. BMC Ophthalmol., 4.","DOI":"10.1186\/1471-2415-4-16"},{"key":"ref_69","unstructured":"Thai, T., Salisbury, B.H., and Zito, P.M. (2021). Ciprofloxacin, StatPearls."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3579\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:33Z","timestamp":1760169093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,18]]},"references-count":69,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123579"],"URL":"https:\/\/doi.org\/10.3390\/cells10123579","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,18]]}}}