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Reena Malongil Bapputty, Ramaprasad Talahalli, Rose Anne Gubitosi-Klug; Montelukast modulates the NF-kB inflammatory cascade in mouse retinal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):190.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal inflammation regulated by nuclear factor-kB (NF-kB) has been implicated in the pathogenesis of diabetic retinopathy. In the current study, we investigated the pharmacologic effects of the anti-inflammatory medication montelukast on the regulation of NF-kB and its downstream transcriptional target ICAM1 in mouse retinal endothelial cells (mREC).
Mouse retinal endothelial cells were cultured in physiologic and 25 mM glucose conditions and treated with TNFa in the presence or absence of montelukast. Western blots evaluated relative levels of phosphorylated/unphosphorylated NF-kB and inhibitor of NF-kB alpha (IkBa).
When mREC were treated with TNFa, an increase in phosphorylated NF-kB levels as well as IkBa levels were detected, signaling activation of this inflammatory cascade and translocation of NF-kB to the nucleus for effects on gene transcription. Indeed, addition of TNFa to mREC significantly increased ICAM1 levels (p<0.05) compared to mREC alone. The presence of montelukast prevented the rise in phosphorylated NF-kB and IkBa levels in a dose-dependent manner, with standard therapy doses of 2 uM montelukast dampening relative phosphorylation of these inflammatory mediators by over 50% compared to mREC without montelukast addition (p<0.05). ICAM1 levels were also reduced with exposure to montelukast, but less significantly suggesting multiple inputs into the regulation of ICAM1 production in mREC under diabetic-like conditions.
Montelukast inhibits the NF-B inflammatory cascade in mREC and may be useful for the treatment of inflammation during early diabetic retinopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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