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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

Lornoxicam treatment decreases the severity of recurrent herpetic stromal keratitis. Latently infected mice were consecutively treated with 0.4 mg/kg of lornoxicam (LOR) or an equal volume of saline on one day before UVB exposure and repeated on the following six days post-UVB exposure. The mean score of corneal opacity in LOR-treated mice (HSK+LOR) was significantly lower than that in the saline control mice (HSK), reaching significance on days 7 to day 21 (p=0.09). The asterisk indicates that p<0.001 when compared to the HSK group at the corresponding time points.
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f1: Lornoxicam treatment decreases the severity of recurrent herpetic stromal keratitis. Latently infected mice were consecutively treated with 0.4 mg/kg of lornoxicam (LOR) or an equal volume of saline on one day before UVB exposure and repeated on the following six days post-UVB exposure. The mean score of corneal opacity in LOR-treated mice (HSK+LOR) was significantly lower than that in the saline control mice (HSK), reaching significance on days 7 to day 21 (p=0.09). The asterisk indicates that p<0.001 when compared to the HSK group at the corresponding time points.

Mentions: As shown in Table 1, on day 7 after UVB irradiation, the development of stromal disease was detected in 67.1% (47/70) of the mice in the saline-treated group but only 38.6% (27/70) in the LOR-treated group. This difference was statistically significant (p=0.001). Similar results were obtained on day 4 after UVB irradiation (Table 1). Moreover, significant corneal opacity was observed in reactivated eyes of mice treated with saline. In contrast, mice receiving LOR demonstrated a significant reduction in clinical scores compared to the saline-treated group (Figure 1). Although 82.86% of the saline-treated eyes developed clinically evident lesions (score 3 or greater) at day 14 after recurrence, only 13.33% of eyes treated with LOR developed such lesions. Mock-infected mice after UVB irradiation developed mild and transient opacity, which disappeared within four days (data not shown). Taken together, these results indicate that LOR reduced the development of keratitis via inhibition of inflammation.


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)

Lornoxicam treatment decreases the severity of recurrent herpetic stromal keratitis. Latently infected mice were consecutively treated with 0.4 mg/kg of lornoxicam (LOR) or an equal volume of saline on one day before UVB exposure and repeated on the following six days post-UVB exposure. The mean score of corneal opacity in LOR-treated mice (HSK+LOR) was significantly lower than that in the saline control mice (HSK), reaching significance on days 7 to day 21 (p=0.09). The asterisk indicates that p<0.001 when compared to the HSK group at the corresponding time points.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Lornoxicam treatment decreases the severity of recurrent herpetic stromal keratitis. Latently infected mice were consecutively treated with 0.4 mg/kg of lornoxicam (LOR) or an equal volume of saline on one day before UVB exposure and repeated on the following six days post-UVB exposure. The mean score of corneal opacity in LOR-treated mice (HSK+LOR) was significantly lower than that in the saline control mice (HSK), reaching significance on days 7 to day 21 (p=0.09). The asterisk indicates that p<0.001 when compared to the HSK group at the corresponding time points.
Mentions: As shown in Table 1, on day 7 after UVB irradiation, the development of stromal disease was detected in 67.1% (47/70) of the mice in the saline-treated group but only 38.6% (27/70) in the LOR-treated group. This difference was statistically significant (p=0.001). Similar results were obtained on day 4 after UVB irradiation (Table 1). Moreover, significant corneal opacity was observed in reactivated eyes of mice treated with saline. In contrast, mice receiving LOR demonstrated a significant reduction in clinical scores compared to the saline-treated group (Figure 1). Although 82.86% of the saline-treated eyes developed clinically evident lesions (score 3 or greater) at day 14 after recurrence, only 13.33% of eyes treated with LOR developed such lesions. Mock-infected mice after UVB irradiation developed mild and transient opacity, which disappeared within four days (data not shown). Taken together, these results indicate that LOR reduced the development of keratitis via inhibition of inflammation.

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