LAUSR

HighlightsSQSTM1/p62 is required for the production of IL‐8 upon IL‐1&bgr; exposure.Absence of SQSTM1/p62 promotes the production of MCP‐1.SQSTM1/p62 has no role in the regulation of IL‐6 in RPE cells.Dysfunctional autophagy increases IL‐8 and decreases MCP‐1 and IL‐6 release from RPE cells.The presence of SQSTM1/p62 plays a role in the production of chemokines in human RPE cells. ABSTRACT Age‐related macular degeneration (AMD) is a complex eye disease in which decline in autophagy leads to the accumulation of sequestosome 1/p62 (SQSTM1/p62)‐labeled waste material inside the retinal pigment epithelial (RPE) cells, and the condition results in activation of the inflammasome signaling and IL‐1&bgr; secretion. Here, we have studied the role of SQSTM1/p62 in the production of IL‐6, IL‐8, and MCP‐1 in the presence or absence of IL‐1&bgr;. SQSTM1/p62 was either overexpressed or silenced in ARPE‐19 cells, which were then exposed to IL‐1&bgr;. Alternatively, bafilomycin A was used to demonstrate the functional decline of autophagy with increased SQSTM1/p62 levels. The protein concentration of SQSTM1/p62 was measured using the western blot technique, and interleukin levels were determined by ELISA. In IL‐1&bgr;‐loaded RPE cells, SQSTM1/p62 depletion and overexpression increased the production of MCP‐1 and IL‐8, respectively. Neither knock‐down nor overexpression of SQSTM1/p62 induced the release of IL‐6. Our data suggest that SQSTM1/p62 is a significant factor in inflammatory responses, especially following the inflammasome activation.