Defensins In Ocular Immunity

<p>Corneal infection with P. aeruginosa results in corneal perforation in susceptible</p> <p>B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal</p> <p>infection, and their potential synergy. Immunostaining and real-time RT-PCR data</p> <p>demonstrated that their expression was either constitutive (mBD1 and mBD2) or</p> <p>inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately</p> <p>regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA</p> <p>treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in</p> <p>ocular defense. Moreover, in vivo studies demonstrated individual and combined effects</p> <p>of mBD2 and mBD3 that modulate bacterial load, PMN infiltration, and production of</p> <p>pro-inflammatory molecules (e.g., IFN-gamma, MIP-2, IL-1beta, TNF-alpha), iNOS, as well as TLR signaling molecules (e.g., TLR2, TLR4, MyD88) and transcription factor NF-kappaB. Most</p> <p>notably, bacterial load was increased at 5 days p.i. by silencing either mBD2 or mBD3,</p> <p>but was elevated at both 1 and 5 days p.i. when silencing both defensins. PMN</p> <p>infiltration was increased at 1 day p.i. by silencing both defensins or mBD3, but not</p> <p>mBD2 alone. iNOS expression was elevated by silencing mBD2, but reduced after</p> <p>silencing mBD3 or both defensins. Additionally, cell sources of mBD2 and mBD3 in</p> <p>corneal stroma were identified by dual label immunostaining after infection: PMN</p> <p>produce both defensins, whereas macrophages and fibroblasts produce mBD2 but not mBD3.</p> <p>Collectively, the data provide evidence that mBD2 and mBD3 together promote</p> <p>resistance against corneal infection. The conclusions may be relevant to potential</p> <p>treatment of other ocular diseases, in addition to P. aeruginosa keratitis.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Anatomy and Cell Biology

Year dc:date.available

2010

Author dc:creator

• Wu, Minhao

Contributors dc:contributor

• Linda D. Hazlett

• cornea
• defensin
• immunity
• infection
• ocular
• TLR
• Medical Immunology
• Ophthalmology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/55

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1054