Abstract
Endogenous carbon monoxide (CO) exerts anti-inflammatory effects. Tristetraprolin (TTP) is known to destabilize pro-inflammatory transcripts. Here we found that exogenous CO enhanced the decay of TNF-α mRNA and suppressed TNF-α expression in LPS-activated macrophages from wild-type (WT) mice. However, TTP deficiency abrogated the effects of exogenous CO. While CO treatment prior to DSS administration in WT mice significantly reduced inflammatory cytokine levels and colitis, it failed to reduce the pro-inflammatory cytokine levels and colitis in TTP knockout (KO) mice. Our results demonstrate that TTP is a key factor mediating the anti-inflammatory action of CO in DSS-induced colitis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents / pharmacology*
-
Carbon Monoxide / pharmacology*
-
Cell Line
-
Colitis / chemically induced
-
Colitis / metabolism*
-
Colitis / prevention & control*
-
Dextran Sulfate / adverse effects*
-
Female
-
Gene Expression Regulation / drug effects
-
Gene Knockout Techniques
-
Macrophages / drug effects
-
Macrophages / metabolism
-
Male
-
Mice
-
Organometallic Compounds / pharmacology
-
RNA Stability / drug effects
-
RNA, Messenger / chemistry
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Tristetraprolin / deficiency
-
Tristetraprolin / genetics
-
Tristetraprolin / metabolism*
-
Tumor Necrosis Factor-alpha / genetics
Substances
-
Anti-Inflammatory Agents
-
Organometallic Compounds
-
RNA, Messenger
-
Tristetraprolin
-
Tumor Necrosis Factor-alpha
-
tricarbonyldichlororuthenium (II) dimer
-
Carbon Monoxide
-
Dextran Sulfate
Grants and funding
This study was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) (2012M3A9C3048687). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.