Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye

Paiva, Cintia S. de; Corrales, Rosa M.; Villarreal, Arturo; Farley, William J.; Li, Dequan; Stern, Michael E.; Pflugfelder, Stephen C.

doi:10.1016/j.exer.2006.02.004

Cited by 379 publications

(317 citation statements)

References 46 publications

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“…6 Increased MMP-9 was observed in an experimental murine model of dry eye, in which it was associated with alteration in corneal surface regularity and epithelial barrier function. [7][8][9][10][11] Increased MMP-9 levels were also observed in the tear fluid of patients with dry eye syndrome. 7,10,12 Hence, MMP-9 was suggested to be responsible for the cellular responses in dry eye syndrome, but the factors behind its deregulated production have not been determined.…”

mentioning

confidence: 84%

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

Huet

Vallée

Delbé

et al. 2011

The American Journal of Pathology

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Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMPmediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. (Am J Pathol

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mentioning

confidence: 84%

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

Huet

Vallée

Delbé

et al. 2011

The American Journal of Pathology

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“…Fourweek-old male mice served as young controls (4W). Sixteen-week-old male mice were untreated (16W) or subjected to desiccating stress by exposure to an air draft with a fan, without (F) or with (FS) subcutaneous injection of 0.5 mg/0.2 mL of the muscarinic receptor blocker, scopolamine hydrobromide (Sigma-Aldrich, St. Louis, MO) in alternating hindquarters four times a day (8 am, 11 am, 2 pm and 5 pm), as previously reported [9,18]. Mice were euthanized after 5 or 10 days (D) of treatment.…”

Section: Animalsmentioning

confidence: 99%

“…Corneal smoothness was assessed by measuring the distortion of a white ring reflected off the corneal epithelium in digital images, as previously described [7]. Corneal epithelial permeability to OGD was assessed by grading the severity of corneal staining with this fluorescent dye, as previously described [18].…”

Section: Corneal Smoothness and Permeabilitymentioning

confidence: 99%

“…In situ zymography was performed to localize the gelatinase activity in the cornea and conjunctiva, as previously described [18]. Cryosections from 4 mice per each group were thawed and incubated overnight with reaction buffer (0.05M Tris-HCl, 0.15M NaCl, 5mM CaCl 2 , and 0.2 mM NaN 3 ; pH 7.6), containing 40 μg/mL FITC-labeled DQ gelatin, which was available in a gelatinase/collagenase assay kit (EnzChek Molecular Probes, Eugene, OR).…”

Section: In Situ Zymographymentioning

confidence: 99%

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Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Yoon

Paiva

et al. 2008

Journal of Autoimmunity

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The non-obese diabetic (NOD) mouse is prone to develop autoimmune disease, including Sjögren's syndrome. The purpose of this study was to determine if desiccating environmental stress exacerbates the development of Sjögren's syndrome-like lacrimal keratoconjunctivitis in the NOD.B10.H2 b mouse. Four-week-old male mice were used as young controls. Sixteen-week-old male mice were untreated or subjected to desiccating stress with a fan alone or with a fan plus subcutaneous injections of the anticholinergic agent scopolamine for 5 or 10 days to inhibit tear production. Mice spontaneously developed Sjögren's syndrome-like lacrimal keratoconjunctivitis as they aged. Desiccating stress increased CD4+ and CCR5+ cells and decreased CD8+ cells in the conjunctival epithelium and lacrimal gland. Intraepithelial γδ T cells significantly decreased after 5 days and returned to baseline levels after 10 days in both groups exposed to desiccating stress. These immunopathological changes were accompanied by a decrease in conjunctival goblet cell density. Greater matrix metalloproteinase-9 production, gelatinase activity and loss of epithelial cell membrane CD25 immunoreactivity was noted in the ocular surface epithelia of stressed mice. These findings indicate that desiccating environmental stress aggravates Sjögren's syndrome-like lacrimal keratoconjunctivitis in the NOD mouse which has defective immunoregulation.

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“…6 Although the exact mechanism of DES is not yet completely understood, there is increasing evidence to suggest that DES is the result of chronic inflammation and underlying cytokines. [7][8][9] Disease or dysfunction of the tear secretory glands leads to changes in tear composition, such as hyperosmolarity, which stimulate the production of inflammatory mediators on the ocular surface. 10 In turn, inflammation may cause dysfunction or disappearance of the cells responsible for tear secretion or retention.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

et al. 2015

Eye

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Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye

Cited by 379 publications

References 46 publications

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

Desiccating environmental stress exacerbates autoimmune lacrimal keratoconjunctivitis in non-obese diabetic mice

Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

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