Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model

Choul Yong Park, Wenjuan Zhuang, Kaevalin Lekhanont, Cheng Zhang, Marisol Cano, Woo Seok Lee, Peter L. Gehlbach, Roy S. Chuck

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the effect of keratoconjunctivitis sicca, induced by botulinum toxin-B (BTX-B), on the inflammatory cytokine gene expression in the lacrimal gland (LG). And to determine the effect of various topical anti-inflammatory agents on the resulting cytokine levels. Methods: Forty-two mice (eight-week-old, female, CBA/J) were divided into six groups. Four groups were injected with BTX-B into both lacrimal glands, one group was injected with saline into both LG (Sal, n=7), and one group served as an uninjected control (Con, n=7). The four groups of BTX-B injected mice were then assigned to a treatment group: 1. no additional treatment (BTX), 2. artificial tear treatment (AT), 3. Cyclosporine A (CSA) treatment, and 4. fluorometholone (FM) treatment (n=7 in each group). Corneal fluorescein staining was evaluated one, two, and four weeks after injection. LGs were harvested after two weeks (groups Con, Sal, and BTX) and four weeks (groups AT, CSA, and FM) after injection. Gene microarray analysis for inflammatory cytokines and their receptors, real time reverse-transcriptase polymerase chain reaction (RT-PCR), and immunofluorescent staining with anti-mouse CD3e monoclonal antibody were then performed on LG tissue. Results: BTX-B injection into the LG effectively induced dry eye in mice two and four weeks following injection. Microarray data identified the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-12, and macrophage migration inhibitory factor (MIF) and the anti-inflammatory cytokines IL-10 and toll-interacting protein (Tollip) as candidates for validation by real time RT-PCR. MIF and IL-12 expression were elevated in BTX-B injected mice at weeks 2 and 4 regardless of treatment. Tollip and IL-1 expressions were increased in some groups after BTX-B injection regardless of the treatment type. Other cytokines showed no significant changes. LG structures were well maintained without significant T lymphocyte infiltration in all groups. Conclusions: Ocular surface change induced by BTX-B injection resulted in an altered expression of various inflammatory cytokines in our murine dry eye model. Alteration of the pathology-induced cytokine profile by topical therapy is reported.

Original languageEnglish (US)
Pages (from-to)2222-2232
Number of pages11
JournalMolecular Vision
Volume13
StatePublished - Nov 29 2007
Externally publishedYes

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Lacrimal Apparatus
Cytokines
Gene Expression
Injections
Fluorometholone
Therapeutics
Interleukin-12
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-1
Cyclosporine
Real-Time Polymerase Chain Reaction
Anti-Inflammatory Agents
Keratoconjunctivitis Sicca
Staining and Labeling
Macrophage Migration-Inhibitory Factors
rimabotulinumtoxinB
Cytokine Receptors
Microarray Analysis
Fluorescein
Interleukin-10

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model. / Park, Choul Yong; Zhuang, Wenjuan; Lekhanont, Kaevalin; Zhang, Cheng; Cano, Marisol; Lee, Woo Seok; Gehlbach, Peter L.; Chuck, Roy S.

In: Molecular Vision, Vol. 13, 29.11.2007, p. 2222-2232.

Research output: Contribution to journalArticle

Park, CY, Zhuang, W, Lekhanont, K, Zhang, C, Cano, M, Lee, WS, Gehlbach, PL & Chuck, RS 2007, 'Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model', Molecular Vision, vol. 13, pp. 2222-2232.
Park, Choul Yong ; Zhuang, Wenjuan ; Lekhanont, Kaevalin ; Zhang, Cheng ; Cano, Marisol ; Lee, Woo Seok ; Gehlbach, Peter L. ; Chuck, Roy S. / Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model. In: Molecular Vision. 2007 ; Vol. 13. pp. 2222-2232.
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abstract = "Purpose: To determine the effect of keratoconjunctivitis sicca, induced by botulinum toxin-B (BTX-B), on the inflammatory cytokine gene expression in the lacrimal gland (LG). And to determine the effect of various topical anti-inflammatory agents on the resulting cytokine levels. Methods: Forty-two mice (eight-week-old, female, CBA/J) were divided into six groups. Four groups were injected with BTX-B into both lacrimal glands, one group was injected with saline into both LG (Sal, n=7), and one group served as an uninjected control (Con, n=7). The four groups of BTX-B injected mice were then assigned to a treatment group: 1. no additional treatment (BTX), 2. artificial tear treatment (AT), 3. Cyclosporine A (CSA) treatment, and 4. fluorometholone (FM) treatment (n=7 in each group). Corneal fluorescein staining was evaluated one, two, and four weeks after injection. LGs were harvested after two weeks (groups Con, Sal, and BTX) and four weeks (groups AT, CSA, and FM) after injection. Gene microarray analysis for inflammatory cytokines and their receptors, real time reverse-transcriptase polymerase chain reaction (RT-PCR), and immunofluorescent staining with anti-mouse CD3e monoclonal antibody were then performed on LG tissue. Results: BTX-B injection into the LG effectively induced dry eye in mice two and four weeks following injection. Microarray data identified the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-12, and macrophage migration inhibitory factor (MIF) and the anti-inflammatory cytokines IL-10 and toll-interacting protein (Tollip) as candidates for validation by real time RT-PCR. MIF and IL-12 expression were elevated in BTX-B injected mice at weeks 2 and 4 regardless of treatment. Tollip and IL-1 expressions were increased in some groups after BTX-B injection regardless of the treatment type. Other cytokines showed no significant changes. LG structures were well maintained without significant T lymphocyte infiltration in all groups. Conclusions: Ocular surface change induced by BTX-B injection resulted in an altered expression of various inflammatory cytokines in our murine dry eye model. Alteration of the pathology-induced cytokine profile by topical therapy is reported.",
author = "Park, {Choul Yong} and Wenjuan Zhuang and Kaevalin Lekhanont and Cheng Zhang and Marisol Cano and Lee, {Woo Seok} and Gehlbach, {Peter L.} and Chuck, {Roy S.}",
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T1 - Lacrimal gland inflammatory cytokine gene expression in the botulinum toxin B-induced murine dry eye model

AU - Park, Choul Yong

AU - Zhuang, Wenjuan

AU - Lekhanont, Kaevalin

AU - Zhang, Cheng

AU - Cano, Marisol

AU - Lee, Woo Seok

AU - Gehlbach, Peter L.

AU - Chuck, Roy S.

PY - 2007/11/29

Y1 - 2007/11/29

N2 - Purpose: To determine the effect of keratoconjunctivitis sicca, induced by botulinum toxin-B (BTX-B), on the inflammatory cytokine gene expression in the lacrimal gland (LG). And to determine the effect of various topical anti-inflammatory agents on the resulting cytokine levels. Methods: Forty-two mice (eight-week-old, female, CBA/J) were divided into six groups. Four groups were injected with BTX-B into both lacrimal glands, one group was injected with saline into both LG (Sal, n=7), and one group served as an uninjected control (Con, n=7). The four groups of BTX-B injected mice were then assigned to a treatment group: 1. no additional treatment (BTX), 2. artificial tear treatment (AT), 3. Cyclosporine A (CSA) treatment, and 4. fluorometholone (FM) treatment (n=7 in each group). Corneal fluorescein staining was evaluated one, two, and four weeks after injection. LGs were harvested after two weeks (groups Con, Sal, and BTX) and four weeks (groups AT, CSA, and FM) after injection. Gene microarray analysis for inflammatory cytokines and their receptors, real time reverse-transcriptase polymerase chain reaction (RT-PCR), and immunofluorescent staining with anti-mouse CD3e monoclonal antibody were then performed on LG tissue. Results: BTX-B injection into the LG effectively induced dry eye in mice two and four weeks following injection. Microarray data identified the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-12, and macrophage migration inhibitory factor (MIF) and the anti-inflammatory cytokines IL-10 and toll-interacting protein (Tollip) as candidates for validation by real time RT-PCR. MIF and IL-12 expression were elevated in BTX-B injected mice at weeks 2 and 4 regardless of treatment. Tollip and IL-1 expressions were increased in some groups after BTX-B injection regardless of the treatment type. Other cytokines showed no significant changes. LG structures were well maintained without significant T lymphocyte infiltration in all groups. Conclusions: Ocular surface change induced by BTX-B injection resulted in an altered expression of various inflammatory cytokines in our murine dry eye model. Alteration of the pathology-induced cytokine profile by topical therapy is reported.

AB - Purpose: To determine the effect of keratoconjunctivitis sicca, induced by botulinum toxin-B (BTX-B), on the inflammatory cytokine gene expression in the lacrimal gland (LG). And to determine the effect of various topical anti-inflammatory agents on the resulting cytokine levels. Methods: Forty-two mice (eight-week-old, female, CBA/J) were divided into six groups. Four groups were injected with BTX-B into both lacrimal glands, one group was injected with saline into both LG (Sal, n=7), and one group served as an uninjected control (Con, n=7). The four groups of BTX-B injected mice were then assigned to a treatment group: 1. no additional treatment (BTX), 2. artificial tear treatment (AT), 3. Cyclosporine A (CSA) treatment, and 4. fluorometholone (FM) treatment (n=7 in each group). Corneal fluorescein staining was evaluated one, two, and four weeks after injection. LGs were harvested after two weeks (groups Con, Sal, and BTX) and four weeks (groups AT, CSA, and FM) after injection. Gene microarray analysis for inflammatory cytokines and their receptors, real time reverse-transcriptase polymerase chain reaction (RT-PCR), and immunofluorescent staining with anti-mouse CD3e monoclonal antibody were then performed on LG tissue. Results: BTX-B injection into the LG effectively induced dry eye in mice two and four weeks following injection. Microarray data identified the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-12, and macrophage migration inhibitory factor (MIF) and the anti-inflammatory cytokines IL-10 and toll-interacting protein (Tollip) as candidates for validation by real time RT-PCR. MIF and IL-12 expression were elevated in BTX-B injected mice at weeks 2 and 4 regardless of treatment. Tollip and IL-1 expressions were increased in some groups after BTX-B injection regardless of the treatment type. Other cytokines showed no significant changes. LG structures were well maintained without significant T lymphocyte infiltration in all groups. Conclusions: Ocular surface change induced by BTX-B injection resulted in an altered expression of various inflammatory cytokines in our murine dry eye model. Alteration of the pathology-induced cytokine profile by topical therapy is reported.

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