ABSTRACT
OBJECTIVES: Synovial fluids of rheumatoid arthritis (RA) patients commonly contain high concentrations of soluble CD14 (sCD14). To investigate its potential role in RA pathogenesis, we tested whether sCD14 binding transmits a signal to fibroblast-like synoviocytes from RA patients (RA-FLS). METHODS: The induction of pro-inflammatory cytokines, chemokines, and mediators by sCD14 stimulation of RA-FLS was quantified by real-time PCR and ELISA. Cell proliferation was assessed by the BrdU assay. LPS-RS, a Toll-like receptor 4 (TLR-4) antagonist, was used to block TLR-4 signaling. RESULTS: Soluble CD14 induced the expression of IL-6 mRNA and secretion of the protein. The expression of other pro-inflammatory cytokines and mediators, such as TNF-α, IL-8, intercellular adhesion molecule-1 (ICAM-1), MMP-3, and RANK ligand (RANKL), was also induced by sCD14. In addition, sCD14 stimulation promoted RA-FLS proliferation. LPS-RS abolished IL-6, IL-8, and ICAM-1 mRNA induction by sCD14 in RA-FLS. On the other hand, TNF-α and IL-17A increased TLR-4 expression by RA-FLS and amplified their sCD14-induced IL-6 expression. CONCLUSIONS: Soluble CD14 transmits inflammatory signals to RA-FLS via TLR-4. The effects of sCD14 may be augmented in inflammatory milieu. Our results suggest that sCD14 is involved in the pathogenesis of RA and may be a novel therapeutic target.
Subject(s)
Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Cytokines/metabolism , Fibroblasts/pathology , Inflammation Mediators/metabolism , Lipopolysaccharide Receptors/metabolism , Synoviocytes/pathology , Toll-Like Receptor 4/metabolism , Cell Proliferation/drug effects , Chemokines/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Interleukin-17/pharmacology , Interleukin-6/metabolism , Interleukin-8/metabolism , Solubility , Synoviocytes/drug effects , Synoviocytes/metabolism , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
AIM: Subjective well-being (SWB) is a psychological construct that is synonymous with happiness. Many variables including age, sex, income, employment, and marital status are related to SWB. Health is also an important determinant of SWB that can be adversely affected in patients with chronic conditions such as rheumatoid arthritis (RA). In this study, we evaluate the SWB of RA patients and compare it with that of healthy controls. METHODS: We obtained the original dataset from the "Quality of Life Survey, 2013", which was conducted by the Economic and Social Research Institute, Cabinet Office, Government of Japan. In this survey, SWB was determined by asking participants to rate their happiness between 0 (very unhappy) and 10 (very happy). The survey also included a 56-point questionnaire regarding well-being-related variables. This questionnaire was administered to RA patients recruited from Kobe University Hospital, and clinical and treatment data were simultaneously collected. RESULTS: Multivariate analysis revealed that RA patients with high or moderate disease activity had SWB scores that were similar to those of controls. However, the SWB scores of RA patients in remission or with low disease activity were higher than those of controls (P = .013). SWB was associated with household income, self-assessment of living costs, self-assessment of health, depression/ anxiety, and social connection. CONCLUSIONS: For RA patients, achieving the therapeutic target can result in better SWB than that of healthy controls. Financial status, self-assessment of health, psychological stress, and social network are also important determinants for the SWB of RA patients.
Subject(s)
Adaptation, Psychological , Arthritis, Rheumatoid/psychology , Health Status , Marital Status , Quality of Life , Social Welfare/psychology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Japan , Male , Middle Aged , Retrospective Studies , Social Behavior , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
OBJECTIVES: Recent studies have shown that mycophenolate mofetil (MMF) is similar to intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis (LN), but that treatment response may vary according to location and race/ethnicity. Moreover, no studies have been conducted to compare the efficacy of MMF with that of IVC for a Japanese population. We therefore conducted a retrospective study to clarify the efficacy and safety of MMF compared with that of IVC for induction therapy for active LN, classes III and IV, in a Japanese population of 21 patients, 11 of whom received MMF and 10 IVC. METHODS: The primary endpoint was expressed as the percentage of responders, who in turn were defined as the patients who met complete or partial response criteria according to the European consensus statement. The secondary endpoints comprised the renal activity component and serological activity. RESULTS: The primary endpoint was achieved in nine (81.8 %) patients receiving MMF and in four (40.0 %) receiving IVC, with no significant difference between the two groups (p = 0.081), while there was also no significant difference between them in terms of secondary endpoints. However, the MMF group suffered significantly fewer hematologic toxic effects than the IVC group. CONCLUSIONS: MMF may be used as an alternative to IVC for inducing renal remission of LN in Japanese patients.
