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Activation of TLR2 or TLR4 Induces ER Stress Leading to Inflammasome‐mediated IL‐1β Secretion in Monocytes
Author(s) -
Hwang Daniel,
Snodgrass Ryan,
Huang Shurong
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.913.10
Subject(s) - tlr2 , unfolded protein response , tunicamycin , thapsigargin , tlr4 , inflammasome , secretion , microbiology and biotechnology , endocrinology , chemistry , medicine , proinflammatory cytokine , phosphorylation , chop , signal transduction , receptor , biology , inflammation , endoplasmic reticulum
The major dietary saturated fatty acid, palmitic acid (C16:0), can induce activation of blood monocytes mediated through Toll‐like receptor (TLR)‐inflammasome signaling pathways. Activated monocytes extravasate into adipose tissues and are differentiated into macrophages or dendritic cells that generate proinflammatory signals leading to insulin resistance. A recent study showed elevated expression of ER stress markers in circulating blood monocytes of patients with type 2 diabetes. Thus, we determined whether agonists of TLR2 and TLR4 (Pam 3 CSK 4 and LPS, respectively) and C16:0 can induce ER stress, and whether ER stress is sufficient to induce monocyte activation as assessed by inflammasome‐mediated IL‐1β secretion. C16:0 induced phosphorylation of IRE‐1 and eIF2 and the expression of CHOP. Pam 3 CSK 4 induced phosphorylation of eIF2 to a lesser extent than did LPS or C16:0, but did not induce phosphorylation of IRE‐1 or CHOP expression. LPS also failed to induce CHOP but induced the phosphorylation of both IRE‐1 and eIF2. These results suggest that activation of TLR2 or TLR4 induces different ER stress responses as assessed by IRE1, eIF2, and CHOP. C16:0‐, Pam 3 CSK 4 ‐, or LPS‐induced IL‐1β production in THP‐1 cells was inhibited by 4‐phenylbutyric acid, an inhibitor of ER stress. Two ER stress‐inducing molecules thapsigargin and tunicamycin induced ER stress; however, thapsigargin but not tunicamycin led to the expression of pro‐IL‐1β and secretion of IL‐1β in THP‐1 cells. Together, these results suggest that not all types of ER stress are sufficient to induce inflammasome‐mediated IL‐1β secretion in THP‐1 monocytes (USDA‐ARS‐WHNRC Program Funds,USDA/NIFA grant 2013‐03477).