Session Information
Date: Monday, November 9, 2015
Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis II
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose:
TIARP (TNFα-induced adipose-related protein) is dominantly expressed in macrophages (Mφ), neutrophils (PMN) and fibroblast-like synoviocytes (FLS). Recently, we found that TIARP functions as a negative regulator in autoimmune arthritis through the suppression of IL-6 production, NF-κB, STAT3 signaling in Mφ, although the molecular mechanism of TIARP-expressing cells in arthritis remains uncertain. The purpose of this study is to elucidate the functional role of TIARP in the pathogenesis of arthritis, especially focusing on PMN and FLS.
Methods:
(1) K/BxN serum-transferred arthritis was induced to TIARP-/-or WT, then the ankle thickness was monitored. Mice were also treated with intravenous administration of anti-Gr1 Ab (for the depletion of PMN) or control Ab every other day after the induction of arthritis. (2) RNAs were extracted from TIARP-/-or WT PMN, subsequently compared by Gene chip. (3) The expression of CXCR1 and CXCR2 on PMN was analyzed, and the chemoattractant activity of TIARP-/- or WT PMN was tested by trans-well chemotaxis assays. (4) Using TIARP-/-or WT FLS, the expression of IL-6, TNFα and CXCL2 after TNFα stimulation were compared. (5) To verify the effect of CXCL2, we performed the chemotaxis assay of PMN by applying to the lower chamber with anti-CXCL2 Ab. (6) The production of IL-17, TNFa and IL-6 from PMN stimulated by immune-complex (IC) were measured by ELISA. (7) Anti-IL-6R Ab was administrated every other day after the induction of serum transferred arthritis.
Results:
(1) The severity of arthritis in TIARP-/- mice was markedly exacerbated, and the recruitment of PMN into the joint was significantly enhanced. TIARP-/-mice treated with anti-Gr1 Ab showed significantly reduced cellular infiltrate into the joint, and reduced synovial thickening. (2) Gene ontology analysis of up-regulated genes in TIARP-/-PMN demonstrated the enrichment of genes involved in chemotaxis. (3) The expression of CXCR1/2 was significantly higher in TIARP-/- PMN, and the recruitment capacity was enhanced. (4) The expressions of IL-6 and CXCL2 in TIARP-/- FLS were significantly higher than in WT, whereas RANKL, MMP3 and MMP9 were not different. (5) The numbers of migrated PMN were significantly decreased by the addition of anti-CXCL2 Ab. (6) The production of IL-17, TNFa and IL-6 were comparable between WT and TIARP-/-PMN. (7) Serum-transferred arthritis in TIARP-/- mice was attenuated by the blockade of IL-6R signaling, and recruitment of PMN into the joint of TIARP-/-mice was suppressed.
Conclusion:
TIARP might down-regulate the production of CXCL2 from FLS and the expression of CXCR1/2 in PMN, resulting in the protective ability of neutrophil migration in arthritic joints, probably via the inhibition of IL-6 signaling.
To cite this abstract in AMA style:
Inoue A, Matsumoto I, Tanaka Y, Umeda N, Kawaguchi H, Ebe H, Matsumoto Y, Sumida T. TIARP Attenuates Autoantibody-Mediated Arthritis Via the Suppression of Neutrophil Infiltration into the Joint [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tiarp-attenuates-autoantibody-mediated-arthritis-via-the-suppression-of-neutrophil-infiltration-into-the-joint/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/tiarp-attenuates-autoantibody-mediated-arthritis-via-the-suppression-of-neutrophil-infiltration-into-the-joint/