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Susan K Hannes, Baoying Liu, H Nida Sen, Shayma Jawad, Zhiyu Li, Robert B Nussenblatt; Increased expression of p21 in CD14+ human monocytes correlates with telomere shortening in ocular sarcoidosis patients. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1857.
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Ocular sarcoidosis is a systemic inflammatory granulomatous disease with an ocular manifestation. Recent studies have demonstrated that telomere length in sarcoid patients is significantly decreased when compared to age-matched controls. The aging and replicative shortening of telomeres can lead to telomere dysfunction, which is characterized by the localization of DNA damage response factors at telomere foci. An upregulation of p21, a cyclin dependent kinase inhibitor that functions at the G1/S cell cycle checkpoint, is often a result of the DNA damage in the shortened telomeres. In this study, we sought to investigate whether p21 expression in ocular sarcoidosis patients is increased.
Human peripheral blood mononuclear cells (PBMCs) were isolated from both healthy donors and sarcoid patients using a Ficoll gradient centrifugation protocol. CD14+ monocytes were isolated based on magnetic depletion protocols for positive selection of human monocytes (Miltenyi Biotetc). Western blots against p21 were performed to assess the expression levels of p21, normalized by GAPDH expression among samples. The serum from the peripheral blood was also collected for cytokine expression detection. A THP-1 human leukemic monocyte cell line functioned as a host for the transfection of a p21 vector in order to detect and characterize the effect of over-expressed p21 on monocyte function.
p21 is mainly expressed in the CD14+ subset of monocytes in peripheral blood. The expression of p21 in monocytes is higher in ocular sarcoidosis patients when compared to healthy age-matched controls. The elevated p21 expression correlates with shortened telomere length in ocular sarcoidosis patients.
In this study, we sought to investigate whether p21 expression in ocular sarcoidosis patients is increased. Our study demonstrated a correlation between shortened telomere length and elevated expression of p21 in peripheral monocytes of ocular sarcoidosis patients. This line of information enhances our understanding of disease pathology, and may have implications in the clinical management of ocular sarcoidosis.
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