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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

TNF-α expression in corneas of different groups determined by ELISA. The data are presented as the mean±standard error of results from three independent experiments. ELISA showed a markedly upregulated activity of NF-κB in infected corneas of saline-treated mice (HSK) and LOR-treated mice (HSK+LOR) when compared to levels in the mock-infected cornea (Control). LOR treatment significantly inhibited TNF-α expression in the cornea at each indicated time point. The asterisk indicates that p<0.05 when compared to the control group, and the hash mark denotes that p<0.05 for the HSK+LOR group when compared to the HSK group at the same time point.
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f3: TNF-α expression in corneas of different groups determined by ELISA. The data are presented as the mean±standard error of results from three independent experiments. ELISA showed a markedly upregulated activity of NF-κB in infected corneas of saline-treated mice (HSK) and LOR-treated mice (HSK+LOR) when compared to levels in the mock-infected cornea (Control). LOR treatment significantly inhibited TNF-α expression in the cornea at each indicated time point. The asterisk indicates that p<0.05 when compared to the control group, and the hash mark denotes that p<0.05 for the HSK+LOR group when compared to the HSK group at the same time point.

Mentions: As shown in Figure 3, the kinetics and pattern of elevated TNF-α expression were similar to that of HSV-induced NF-κB activity. The TNF-α expression in all infected groups were significantly higher than that in the mock-infected control, showing a maximal 11.6 fold increase in comparison with the mock-infected control at day 7. In contrast, the production of TNF-α was markedly suppressed by LOR treatment before recurrence. Cornea from the mock-infected mice and from the LOR alone mice showed minimal basal levels of TNF-α expression (p=0.128).


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)

TNF-α expression in corneas of different groups determined by ELISA. The data are presented as the mean±standard error of results from three independent experiments. ELISA showed a markedly upregulated activity of NF-κB in infected corneas of saline-treated mice (HSK) and LOR-treated mice (HSK+LOR) when compared to levels in the mock-infected cornea (Control). LOR treatment significantly inhibited TNF-α expression in the cornea at each indicated time point. The asterisk indicates that p<0.05 when compared to the control group, and the hash mark denotes that p<0.05 for the HSK+LOR group when compared to the HSK group at the same time point.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: TNF-α expression in corneas of different groups determined by ELISA. The data are presented as the mean±standard error of results from three independent experiments. ELISA showed a markedly upregulated activity of NF-κB in infected corneas of saline-treated mice (HSK) and LOR-treated mice (HSK+LOR) when compared to levels in the mock-infected cornea (Control). LOR treatment significantly inhibited TNF-α expression in the cornea at each indicated time point. The asterisk indicates that p<0.05 when compared to the control group, and the hash mark denotes that p<0.05 for the HSK+LOR group when compared to the HSK group at the same time point.
Mentions: As shown in Figure 3, the kinetics and pattern of elevated TNF-α expression were similar to that of HSV-induced NF-κB activity. The TNF-α expression in all infected groups were significantly higher than that in the mock-infected control, showing a maximal 11.6 fold increase in comparison with the mock-infected control at day 7. In contrast, the production of TNF-α was markedly suppressed by LOR treatment before recurrence. Cornea from the mock-infected mice and from the LOR alone mice showed minimal basal levels of TNF-α expression (p=0.128).

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