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Lornoxicam suppresses recurrent herpetic stromal keratitis through down-regulation of nuclear factor-kappaB: an experimental study in mice.

Yin J, Huang Z, Xia Y, Ma F, Zhang LJ, Ma HH, Li Wang L - Mol. Vis. (2009)

Bottom Line: Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis.Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response.Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People's Republic of China.

ABSTRACT

Purpose: We designed the current study to determine the protective effects of lornoxicam, a cyclooxygenase (COX) inhibitor, on recurrent herpetic stromal keratitis (HSK) and the nuclear factor-kappaB (NF-kappaB)-mediated mechanism in mice.

Methods: A corneal latent herpes simplex virus-1 (HSV-1) infected mouse model was established. Six weeks later, Ultraviolet B (UVB) irradiation induced the recurrence. Corneal swabs were obtained and cultured with indicator cells to determine shedding of the virus. Lornoxicam was administered intraperitoneally daily, beginning one day before irradiation and lasting for seven days. Saline-treated and mock-infected control groups were also studied at the same time. Development of corneal inflammation and opacity was scored. Immunohistochemical staining and an electrophoretic mobility shift assay were performed to evaluate the effect of lornoxicam on NF-kappaB activation in the corneal tissues. The levels of tumor necrosis factor-alpha (TNF-alpha) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA).

Results: HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-kappaB and elevated production of TNF-alpha. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response.

Conclusions: Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.

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Related in: MedlinePlus

Influence of LOR on the histopathological and immunohistochemical studies in mouse corneas 14 days after UV irradiation. The typical histologic findings of cornea stained with hematoxylin and eosin (A, B) are shown. A: The cornea in the saline-treated group shows marked inflammation, obvious edema, profound neovascularization, and significant hypercellularity in the stroma. B: The cornea in the LOR-treated group exhibits only scattered inflammatory cells, mild stromal swelling, and less neovascularization. Corneal tissues (C-F) were analyzed by immunohistochemistry to determine the expression of NF-κB. Immunohistochemical staining with an antibody against activated NF-κB was performed to detect the expression of NF-κB. Sections incubated without a primary antibody served as negative controls. All tissue sections were counterstained with hematoxylin. These samples were representative of all corneas examined. Brown staining indicates activated NF-κB. C,D: The cornea in the mock-infected group and the cornea in LOR alone group show that NF-κB activity is only observed very faintly in the base cells of epithelium (arrowheads). E: Recurrence induced wide spread positive staining of NF-κB, which was most robust in the stroma (arrows) of the saline-treated group. F: Scant immunoreactivity of NF-κB was observed in the stroma of the LOR-treated group (arrows). Original magnifications, 400X.
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f4: Influence of LOR on the histopathological and immunohistochemical studies in mouse corneas 14 days after UV irradiation. The typical histologic findings of cornea stained with hematoxylin and eosin (A, B) are shown. A: The cornea in the saline-treated group shows marked inflammation, obvious edema, profound neovascularization, and significant hypercellularity in the stroma. B: The cornea in the LOR-treated group exhibits only scattered inflammatory cells, mild stromal swelling, and less neovascularization. Corneal tissues (C-F) were analyzed by immunohistochemistry to determine the expression of NF-κB. Immunohistochemical staining with an antibody against activated NF-κB was performed to detect the expression of NF-κB. Sections incubated without a primary antibody served as negative controls. All tissue sections were counterstained with hematoxylin. These samples were representative of all corneas examined. Brown staining indicates activated NF-κB. C,D: The cornea in the mock-infected group and the cornea in LOR alone group show that NF-κB activity is only observed very faintly in the base cells of epithelium (arrowheads). E: Recurrence induced wide spread positive staining of NF-κB, which was most robust in the stroma (arrows) of the saline-treated group. F: Scant immunoreactivity of NF-κB was observed in the stroma of the LOR-treated group (arrows). Original magnifications, 400X.

Mentions: As shown in Figure 4, the corneas experiencing recurrent HSK showed significant extracellular edema, pronounced infiltrate, and congestive blood vessels 14 days after irradiation whereas LOR treatment ameliorated the recurrent HSK lesions. A significantly decreased number of inflammatory cells and less neovascularization were observed in the LOR-treated group (Figure 4A,B).


Lornoxicam suppresses recurrent herpetic stromal keratitis through down-regulation of nuclear factor-kappaB: an experimental study in mice.

Yin J, Huang Z, Xia Y, Ma F, Zhang LJ, Ma HH, Li Wang L - Mol. Vis. (2009)

Influence of LOR on the histopathological and immunohistochemical studies in mouse corneas 14 days after UV irradiation. The typical histologic findings of cornea stained with hematoxylin and eosin (A, B) are shown. A: The cornea in the saline-treated group shows marked inflammation, obvious edema, profound neovascularization, and significant hypercellularity in the stroma. B: The cornea in the LOR-treated group exhibits only scattered inflammatory cells, mild stromal swelling, and less neovascularization. Corneal tissues (C-F) were analyzed by immunohistochemistry to determine the expression of NF-κB. Immunohistochemical staining with an antibody against activated NF-κB was performed to detect the expression of NF-κB. Sections incubated without a primary antibody served as negative controls. All tissue sections were counterstained with hematoxylin. These samples were representative of all corneas examined. Brown staining indicates activated NF-κB. C,D: The cornea in the mock-infected group and the cornea in LOR alone group show that NF-κB activity is only observed very faintly in the base cells of epithelium (arrowheads). E: Recurrence induced wide spread positive staining of NF-κB, which was most robust in the stroma (arrows) of the saline-treated group. F: Scant immunoreactivity of NF-κB was observed in the stroma of the LOR-treated group (arrows). Original magnifications, 400X.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2697669&req=5

f4: Influence of LOR on the histopathological and immunohistochemical studies in mouse corneas 14 days after UV irradiation. The typical histologic findings of cornea stained with hematoxylin and eosin (A, B) are shown. A: The cornea in the saline-treated group shows marked inflammation, obvious edema, profound neovascularization, and significant hypercellularity in the stroma. B: The cornea in the LOR-treated group exhibits only scattered inflammatory cells, mild stromal swelling, and less neovascularization. Corneal tissues (C-F) were analyzed by immunohistochemistry to determine the expression of NF-κB. Immunohistochemical staining with an antibody against activated NF-κB was performed to detect the expression of NF-κB. Sections incubated without a primary antibody served as negative controls. All tissue sections were counterstained with hematoxylin. These samples were representative of all corneas examined. Brown staining indicates activated NF-κB. C,D: The cornea in the mock-infected group and the cornea in LOR alone group show that NF-κB activity is only observed very faintly in the base cells of epithelium (arrowheads). E: Recurrence induced wide spread positive staining of NF-κB, which was most robust in the stroma (arrows) of the saline-treated group. F: Scant immunoreactivity of NF-κB was observed in the stroma of the LOR-treated group (arrows). Original magnifications, 400X.
Mentions: As shown in Figure 4, the corneas experiencing recurrent HSK showed significant extracellular edema, pronounced infiltrate, and congestive blood vessels 14 days after irradiation whereas LOR treatment ameliorated the recurrent HSK lesions. A significantly decreased number of inflammatory cells and less neovascularization were observed in the LOR-treated group (Figure 4A,B).

Bottom Line: Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis.Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response.Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People's Republic of China.

ABSTRACT

Purpose: We designed the current study to determine the protective effects of lornoxicam, a cyclooxygenase (COX) inhibitor, on recurrent herpetic stromal keratitis (HSK) and the nuclear factor-kappaB (NF-kappaB)-mediated mechanism in mice.

Methods: A corneal latent herpes simplex virus-1 (HSV-1) infected mouse model was established. Six weeks later, Ultraviolet B (UVB) irradiation induced the recurrence. Corneal swabs were obtained and cultured with indicator cells to determine shedding of the virus. Lornoxicam was administered intraperitoneally daily, beginning one day before irradiation and lasting for seven days. Saline-treated and mock-infected control groups were also studied at the same time. Development of corneal inflammation and opacity was scored. Immunohistochemical staining and an electrophoretic mobility shift assay were performed to evaluate the effect of lornoxicam on NF-kappaB activation in the corneal tissues. The levels of tumor necrosis factor-alpha (TNF-alpha) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA).

Results: HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-kappaB and elevated production of TNF-alpha. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response.

Conclusions: Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.

Show MeSH
Related in: MedlinePlus