Toll-like receptor-4 drives pro-inflammatory cytokine response & tissue degradation in human bacterial keratitis

Hossain, Parwez, Wong, Yuk, Sethu, Claire and Louafi, Fethi (2011) Toll-like receptor-4 drives pro-inflammatory cytokine response & tissue degradation in human bacterial keratitis. Investigative Ophthalmology & Visual Science, 52 (14), [6634].

Abstract

Purpose: : Toll-like Receptor-4 (TLR4) is a key component of the innate immune response during bacterial infections. Pathways and downstream effectors relating to TLR signalling in human bacterial keratitis (BK) remain unknown. By activating the TLR4 signalling cascade with bacterial lipoploysaccharide (LPS), we investigated whether TLR4 influenced matrix metalloproteases (MMP-2, MMP-9) and cytokine expression in diseased human primary corneal fibroblast (CF) cells are altered.

Methods: : Human primary CF cells from patients with severe corneal ulceration from patients with gram negative bacterial keratitis were grown ex vivo and cultured in conjunction with healthy controls. CF cells were treated with exogenous LPS derived from Pseudomonas Aeruginosa.

Results: : TLR4, MMP-2 and MMP-9 were constitutively expressed in both ulcerated and control CF cells. Diseased CF cells showed greater responsiveness to LPS stimulation. TLR4 and MMP-9 expression was dose-dependently increased by LPS. MMP-2 expression was not affected by LPS. Analysis on cytokine expression revealed that IL-2, IL-8, IL-10, IL-12p70, GM-CSF, IFNγ and TNF-α expression increased following LPS treatment but only in the diseased cells.

Conclusions: : TLR4 activation with LPS increases TLR4, MMP-9 and cytokine expression in CF cells cultured from human BK patients. Over expression of these products may provide a local mechanism to eradicate bacterial infection but also contribute to corneal ulceration and perforation. This is the first description of the effect of TLR4 activation in human bacterial keratitis.

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Contributors

Author: Parwez Hossain

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