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M. E. Marin Castano, M. Pons, S. W. Cousins, O. Alcazar; Regulation of MCP-1 by Cigarette Smoke Components and Angiotensin II in Human RPE Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):716.
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Cigarette smoking, hypertension (HTN), and low grade inflammation have been implicated in the pathogenesis of age-related macular degeneration (AMD). MCP-1 is a chemokine synthesized by RPE and is postulated to be responsible for the recruitment of macrophages. Several studies have suggested an association between lack of this chemokine and drusen deposition. We postulate that several tar components of cigarette smoke, such as hydroquinone (HQ), chatecol (CT), and nicotine in combination with HTN, might regulate MCP-1 and contribute to subretinal deposit formation and progression. In this study, we sought to determine the impact of both cigarette smoke-derived toxic chemicals and HTN-associated hormones like angiotensin II (Ang-II) in MCP-1 expression and secretion by RPE.
Confluent cultures of human RPE cells in low serum conditions were incubated with 50 µM quinones (HQ and CT) and nicotine (10-6M and 10-8M) alone or in combination for 6 or 24 hrs.In parallel experiments, RPE cells were first incubated with a) 100 µM HQ for 6 hrs, then washed to remove the drug and 10-7M Ang II added for 24 hrs and b) 10-7M Ang II alone or in combination with its receptor antagonists for 24 hours. Supernatants and cell homogenates were collected to assess MCP-1 mRNA expression by real-time PCR and protein secretion by ELISA.
HQ alone or in combination with CT and/or nicotine decreased MCP-1 expression and secretion by RPE cells after treatment for 6 hours, whereas treatment for 24 hours suppressed this chemokine. No changes were observed after treatment with HQ in combination with Ang II. However, Ang II alone or in combination with its AT2 receptor antagonist increased significantly MCP-1 mRNA and protein secretion.
The diminution and suppression of MCP-1 in RPE cells can be explained through HQ effect, given that the effect of CT or nicotine alone on MCP-1 mRNA and protein remained unaltered. This decline and/or suppression of MCP-1 may decrease macrophage recruitment and consequently clearance and degradation of RPE-derived debris. On the other hand, the upregulation of MCP-1 by Ang II via AT1 may increase recruitment of macrophages. These findings support the hypothesis that cigarette smoke-derived toxic chemicals and Ang II may contribute to subRPE deposits formation and progression.
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