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The Suppressive Effects of Indole‐3‐carbinol (I3C)/3,3′ Diindolylmethane (DIM) on LPS‐induced IL1 Release May Be Associated with Changes in CD84 in THP‐1 Monocytes
Author(s) -
Kim Young,
Wang Thomas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.593.5
Subject(s) - indole test , thp1 cell line , chemistry , pharmacology , medicine , biology , stereochemistry , cell culture , genetics
CD84 is a cell‐surface receptor that belongs to signaling lymphocyte activation molecule (SLAM) family involved in lymphocyte activation. Nevertheless, the expression and regulation of this molecule during developmental stages of monocytes and macrophages are less clear. Here, we report that CD84 may play a role in mediating I3C/DIM suppression of LPS‐induced pro‐inflammatory cytokine IL1 in THP‐1 monocytes but not in phorbol 12‐myristate 13‐acetate (PMA)‐induced macrophages. Human THP‐1 moncytes or PMA‐differentiated THP‐1 macrophages (d‐THP‐1) were treated with or without I3C (0‐50 µM) or DIM (0‐25 µM) for 48 hours. For experiments involved with lipopolysaccharide (LPS)‐induced inflammatory responses, THP1 or d‐THP‐1 was treated with or without LPS for two hours after I3C/DIM treatments. CD84 and 2B4 were found to be the major SLAM proteins expressed in monocytes while CD84 and CRACC was the major species in d‐THP‐1 cells. Exposure to I3C and DIM inhibited the expression of CD84, but neither 2B4 nor CRACC, in THP‐1 monocytes and d‐THP‐1 cells. Interestingly, these differential effects of I3C and DIM on CD84 expression in monocytes and macrophages were co‐related with their suppressive effects on LPS‐induced pro‐inflammatory cytokine IL‐1 expression in these blood cells. Furthermore, the suppressive effects of I3C/DIM on LPS‐induced IL1 levels were correlated with the decreased expression of BCL2 oncogene. There were no changes observed in Bax expression. Hence, I3C and DIM may exert their anti‐inflammatory effects in part through the modulation of immune responses involving CD84 and cytokines. This study was supported by the NIH Interagency Agreement with USDA Y01 N 14001001‐1‐0‐1).