- Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4+Foxp3+ Regulatory T Cells Differentiation. [Journal Article]
- FIFront Immunol 2018; 9:1662
- Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced art...
Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells' frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA.
- Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis. [Journal Article]
- ARAnn Rheum Dis 2018 Jul 30
- CONCLUSIONS: HK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.
- Hematological malignancies mimicking rheumatic syndromes: case series and review of the literature. [Review]
- RIRheumatol Int 2018 Jul 18
- It is well established that some rheumatic syndromes (RS) are associated with several hematological malignancies. We aimed to describe the clinical course of patients with hematological malignancies ...
It is well established that some rheumatic syndromes (RS) are associated with several hematological malignancies. We aimed to describe the clinical course of patients with hematological malignancies mimicking RS. We studied a series of four patients presenting with apparent RS who were eventually diagnosed with hematological malignancies, and reviewed the relevant literature. Our series consisted of 4 patients, with a mean age of 62.8 ± 20.3 years, who presented to our rheumatology unit between December 2012 and March 2018. Two patients were initially diagnosed with polyarthritis. One of these patients was eventually diagnosed with multiple myeloma and amyloidosis and the other was diagnosed with angioimmunoblastic T-cell lymphoma. The third patient was initially diagnosed with migratory arthritis and was eventually diagnosed with acute myeloid leukemia. The fourth patient was initially diagnosed with giant cell arteritis and eventually diagnosed with anaplastic large T-cell lymphoma. All the patients displayed a very good response to corticosteroid treatment. Vigilance for occult malignancy is essential in the diagnostic workup of RS. A good response to corticosteroids may constitute a major diagnostic pitfall in patients with hematological malignancies presenting with an apparent RS. In these cases, subtle clinical and laboratory features should elicit the clinician to seek for an occult malignancy.
- Leukocyte trafficking between stromal compartments: lessons from rheumatoid arthritis. [Review]
- NRNat Rev Rheumatol 2018 Jul 12
- The trafficking of leukocytes from their site of production in the bone marrow through the circulation and into peripheral tissues is a highly coordinated and tightly regulated process in healthy ind...
The trafficking of leukocytes from their site of production in the bone marrow through the circulation and into peripheral tissues is a highly coordinated and tightly regulated process in healthy individuals. Lymphocytes are long-lived cells that visit many lymphoid and peripheral tissues over their lifetime and can even recirculate back to the bone marrow, whereas granulocytes and monocytes are not thought to recirculate so widely. Using rheumatoid arthritis (RA) as an example, this Review explores the migratory journey of leukocytes during the establishment and resolution of disease - from the blood, through the lymphoid tissues and into peripheral sites such as the lungs and the gut before their entry into the synovium. This Review explores our current understanding of differences in the molecular processes that regulate leukocyte trafficking at different phases of disease and in different stromal compartments, which could help to explain the disease heterogeneity seen in patients with RA. Expanding our knowledge of these processes will open new avenues in the clinical management of RA, paving the way for personalized medicine that is founded on the pathological molecular signature of each patient, which varies according to their phase of disease or disease subtype.
- Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts. [Journal Article]
- ARAnn Rheum Dis 2018 Jul 06
- CONCLUSIONS: CD82 could contribute to RASF migration to sites of inflammation and tissue damage, where CD82 keeps aggressive RASF on site.
- Migratory polyarthritis as a paraneoplastic syndrome in a patient with diffuse large B cell lymphoma: a case report. [Journal Article]
- JMJ Med Case Rep 2018 Jun 26; 12(1):189
- CONCLUSIONS: Poor response to routine therapy for inflammatory arthritis should lead to early suspicion of paraneoplastic arthritis which will prompt investigation for an underlying malignancy. Suspicion of carcinomatous polyarthritis should be made in those with migratory polyarthritis and should be thoroughly investigated to exclude underlying malignancy.
- GWAS-identified CCR1 and IL10 loci contribute to M1 macrophage-predominant inflammation in Behçet's disease. [Journal Article]
- ARArthritis Res Ther 2018 Jun 12; 20(1):124
- CONCLUSIONS: The present study reveals that GWAS-identified SNPs contribute to M1 Mφ-predominant inflammation in BD. Our data also suggest that the skewed Mφ polarization is correctable by immunological intervention.
- Inhibitory effects of tubeimoside I on synoviocytes and collagen-induced arthritis in rats. [Journal Article]
- JCJ Cell Physiol 2018 May 15
- Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and ef...
Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and efficacy continues and natural compounds have been considered as alternatives or complementary agents to gain immense attractions. Tubeimoside I (TBMS I), a main triterpenoid saponin isolated from Bolbostemma paniculatum, has been reported to possess antiviral and anticancer effects. However, its effect on RA remains unknown. Here, we investigated the therapeutic effect of TBMS I in collagen-induced arthritis (CIA) rats and explored its underlying mechanism. Our results showed that TBMS I treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. In vitro studies revealed that TBMS I suppressed the production of pro-inflammatory cytokines including IL-1β, IL-6, IL-8 and TNFα, and downregulated the expression of MMP-9. In addition, TBMS I attenuated the destructive phenotypes of FLS of CIA rats including inhibiting proliferation and reducing migration rate. Further mechanistic analysis demonstrated that TBMS I suppressed TNFα-induced activations of NF-κB and MAPKs (p38 and JNK) leading to the downregulation of pro-inflammatory cytokines, which was beneficial to the anti-proliferative and anti-migratory activities of FLS cells. Taken together, TBMS I has a great potential to be developed into a novel therapeutic agent for the treatment of RA.
- TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis. [Journal Article]
- ECEur Cytokine Netw 2018 Mar 01; 29(1):27-35
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migr...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2). We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients' samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.
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- Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitment in vivo. [Journal Article]
- TTheranostics 2018; 8(9):2407-2423
- CONCLUSIONS: We provide a combinatorial approach to rapidly characterize molecular mechanisms of leukocyte recruitment in vivo, with the potential to aid in identification of diagnostic and therapeutic targets in inflammatory pathologies.