Abnormal Iodine Nutrition-Induced ER Stress Upregulates MCP-1 Expression Through P38/MAPK Signaling Pathway in Thyroid Cells

Abstract

Iodine is an important chemical for thyroid hormone synthesis. The association between iodine nutrition status and the risk of disease present U-shaped curve, as either low or high iodine nutrition status will increase the risk of thyroid diseases. Endoplasmic reticulum stress (ER stress), which can induce over expressions of inflammation factors, like monocyte chemo-attractant protein-1 (MCP-1), is related to the pathogenesis of thyroid disease. However, the correlations among iodine, MCP-1 and ER stress are not entirely clear during the pathogenesis of thyroid diseases. Present study aims to investigate how iodine nutrition status influences MCP-1 expression through P38/MAPK pathway as well as the roles of ER stress in this process. Human thyroid cells (Nthy-ori-3-1) was used as a cell model in this study. The expressions of p-P38, PERK, IRE1, ATF6, and MCP-1 were detected after the cells were treated with iodine at different concentrations with or without ER stress inhibitor (4-PBA) or P38/MAPK blocker (SB203580). The expressions of p-P38, PERK, IRE1, ATF6, and MCP-1 in Nthy-ori-3-1 cells treated with iodine at abnormal concentrations were all significantly higher than those in cells treated with iodine at normal concentration. However, addition of ER stress blocker, 4-PBA in the abnormal-iodine treated cells, decreased the expressions of p-P38, PERK, IRE1, ATF6, and MCP-1. Similarly, P38/MAPK activity inhibitor, SB203580, also decreased the expressions of p-P38 and MCP-1. Abnormal iodine nutrition status triggered ER stress and upregulated MCP-1 expression through P38/MAPK signaling pathway in thyrocyte.

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