Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Myeloid cells membrane-bound TREM-1 (mTREM-1) amplifies toll like receptor (TLR)-4-mediated myeloid cells activation, accompanied by release of soluble TREM-1 (sTREM-1) that acts as a decoy receptor. Previous studies suggest an upregulation of mTREM-1 in gout. TGFβ was previously shown to play an anti-inflammatory role in the spontaneous resolution of gout attack. In this study, we aimed to determine the effect of sTREM-1 in gout.
Methods: We’ve used a synthetic peptide inhibitor of TREM-1 (LP17) that is a conserved domain (LQVTDSGLYRCVIYHPP) of the extracellular portion of TREM-1 in an air-pouch mouse model of gout to determine the role of sTREM-1 in MSU crystal (MSUC)-induced inflammation.
Results: MSU crystals injected into the air-pouch induced an increase of mTREM-1 surface expression on CD11b-positive leukocytes by magnitude of 1.77 of (assessed by FACS) (p=0.013, n=3), as well as an increase of exudate sTREM-1 level (assessed by ELISA) by 397.4% (2082.02±630.21 vs. 418.6±323.7pg/ml, n=4, p=0.017). The synthetic peptide inhibitor of TREM-1 (LP17) injected into the air-pouch together with MSU crystals attenuated the inflammatory response by significant reduction of leukocyte count (MSUC+LP17: 0.83×106±6.8 vs. MSUC: 1.92×106±15.9, n = 5, p=0.041) , exudate level of TNFα (MSUC+LP17: 14.5±2.1 vs. MSUC: 27.9±3 pg/ml, n=3, p=0.036) and the chemokine CCL3/MIP1α level (MSUC+LP17: 11.8±8.2 vs. MSUC: 23.7±11.8 pg/ml, p=0.049). In contrast, the exudate level of the anti-inflammatory cytokine TGFβ was not affected by LP17 (PBS: 23.4±31.46pg/ml, MSUC: 123.57±51.96pg/ml, p< 0.0001; MSUC+LP17: 156.72±154.75pg/ml, n=10, p=NS).
Conclusion: Soluble TREM-1 (LP17) ameliorates MSU crystal-induced inflammation through several modes of action, as is demonstrated by significant decrease of exudate leukocyte count, as well as TNFα and CCL3 levels. Moreover, LP17 didn’t change TGFβ level, suggesting synergistic anti-inflammatory effects of sTREM-1 and TGFβ that leads to the resolution of gout attack.
To cite this abstract in AMA style:Kliminski V, Molad Y. Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) Ameliorates Monosodium Urate Crystals (MSUC)-induced Inflammation in a Mouse Air-pouch Model of Gout [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/soluble-triggering-receptor-expressed-on-myeloid-cells-1-strem-1-ameliorates-monosodium-urate-crystals-msuc-induced-inflammation-in-a-mouse-air-pouch-model-of-gout/. Accessed October 31, 2020.
« Back to 2019 ACR/ARP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-triggering-receptor-expressed-on-myeloid-cells-1-strem-1-ameliorates-monosodium-urate-crystals-msuc-induced-inflammation-in-a-mouse-air-pouch-model-of-gout/