Nitric oxide protects cultured rheumatoid synovial cells from Fas‐induced apoptosis by inhibiting caspase‐3

Migita, Kiyoshi; Yamasaki, Satoshi; Kita, Masako; Ida, Hiroaki; Shibatomi, Kazutaka; Kawakami, Atsushi; Aoyagi, Takahiko; Eguchi, Katsuyuki

doi:10.1046/j.1365-2567.2001.01252.x

Cited by 37 publications

(23 citation statements)

References 32 publications

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“…We also found reduced processing of the large subunit of caspase-3 after SNP co-stimulation. Similar observations regarding the effects of NO-donors on CD95-dependent apoptosis were reported for a human T-cell line (Bernassola et al, 2001) and rheumatoid synovial cells (Migita et al, 2001). Consistent with the proposed model for CD95 mediated caspase-3 activation, the initial caspase-8 catalyzed cleavage of procaspase-3 yielded the p22 fragment of the large subunit (Daniel et al, 2001).…”

Section: Discussionsupporting

confidence: 80%

Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis

Kühn

Shikhman

Lotz

2003

Journal Cellular Physiology

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This study addresses mechanisms by which interleukin-1beta (IL-1beta) regulates human chondrocyte apoptosis induced by a combination of the anti-CD95 antibody CH-11 and the proteasome inhibitor (PSI). The effect of IL-1beta on apoptosis varied among tissue samples. IL-1beta either enhanced (16/22 samples) or inhibited (6/22 samples) DNA fragmentation and caspase-3 processing. The protective effect of IL-1beta was abrogated by the nitric oxide (NO) synthesis inhibitor N-monomethyl-l-arginine (L-NMMA) while apoptosis stimulation was not affected. The NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl penicillamine (SNAP) blocked DNA fragmentation, and this was associated with partial inhibition of caspase-3 processing. Pyrrolidine dithiocarbamate (PDTC), a scavenger of reactive oxygen species (ROS) blocked apoptosis induction by CH-11/PSI as well as the enhancement by IL-1beta. The pro-apoptotic effects of IL-1beta were also abrogated by the p38 inhibitor SB 202190. In conclusion, IL-1beta augments CH-11/PSI induced apoptosis in the majority of chondrocyte samples. The pro-apoptotic effect of IL-1beta is not dependent on NO. In contrast, the anti-apoptotic effect of IL-1beta observed in a minority of samples is partially NO-dependent.

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Section: Discussionsupporting

confidence: 80%

Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis

Kühn

Shikhman

Lotz

2003

Journal Cellular Physiology

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“…We compared the PsA patients with subjects affected by RA, an inflammatory disease, in which protein oxidation phenomena play an important pathogenic role. Furthermore, we compared PsA cases with patients affected by OA, commonly used as control by other authors (9,18,29), because of the evidence that oxidative stress does not seem to have a relevant role in this disease (30). The importance of oxidative stress in the joint compartment is confirmed by our finding that levels of SH groups in SF are inversely correlated with the number of WBC and percentage of PMN cells, which are both parameters of local inflammation in SF.…”

Section: Discussionmentioning

confidence: 59%

Protein oxidation markers in the serum and synovial fluid of psoriatic arthritis patients

Firuzi

Spadaro

et al. 2008

Clinical Laboratory Analysis

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The role of oxidative stress has been studied in rheumatoid arthritis (RA) and other inflammatory joint diseases to some extent, but its importance in psoriatic arthritis (PsA) has rarely been investigated. The aim of this study was to analyze the levels of protein oxidation markers, sulfhydryl (SH) and carbonyl (CO) groups, in the synovial fluid (SF) and serum of PsA patients and compare them with the findings in RA and osteoarthritis (OA) patients. A total of 49 subjects with a knee-joint effusion including 16 PsA, 18 RA, and 15 OA patients were studied. In all patients, the levels of SH groups measured in the serum and SF inversely correlated with the number of white blood cells (WBC) (P<0.05) and the percentage of polymorphonuclear leukocytes (PMN) (P<0.01) in SF. Serum SH levels inversely correlated with serum erythrocyte sedimentation rate (ESR) (P<0.02) and C-reactive protein (CRP) (P<0.05) values. The SH levels in SF were significantly lower in patients affected by PsA and RA compared to OA cases (P<0.02). The serum SH levels in PsA were lower than OA (P<0.001) and higher than RA patients (P<0.05). The serum and synovial levels of CO groups in PsA, RA, and OA patients were similar. Our study provides novel evidence on the involvement of protein oxidation in PsA and confirms the important role of oxidative stress in the pathogenesis of RA. These data suggest that antioxidant agents can potentially be a useful addition to the conventional therapy in the management of these diseases.

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“…59 Consistent with this, rheumatoid arthritis is also associated with elevated serum and synovial fluid NO. 60 Migita et al 60 further suggested that synovial hyperplasia in rheumatoid arthritis results from resistance to Fas-mediated apoptosis in the presence of NO, as Fas-mediated apoptosis is suppressed by the addition of a NO donor to synovial cells. Their study further implicates NO in the inhibition of caspase-3 cleavage to its active form.…”

Section: Discussionmentioning

confidence: 99%

IL-15 maintains T-cell survival via S-nitrosylation-mediated inhibition of caspase-3

et al. 2014

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Caspase activity is critical for both T-cell survival and death. However, little is known regarding what determines caspase activity in cycling T cells. Interleukin (IL)-2 and IL-15 confer very different susceptibilities to T-cell death. We therefore considered that IL-2 and IL-15 differentially regulate caspase activity to influence T-cell survival. We observed that IL-2-cultured primary murine effector T cells manifested elevated levels of caspase-3 activity compared with IL-15-cultured T cells. T cell receptor (TCR) restimulation further increased caspase activity and induced considerable cell death in IL-2-cultured T cells, but provoked only a minimal increase of caspase activity and cell death in IL-15-cultured T cells. IL-2 sensitization to cell death was caspase-3 mediated. Interestingly, increased active caspase-3 levels with IL-2 were independent of active initiator caspase-8 and caspase-9 that were similar with IL-2 and IL-15. Rather, caspase-3 activity was inhibited by posttranslational S-nitrosylation in IL-15-cultured T cells, but not in the presence of IL-2. This paralleled increased reactive nitrogen and oxygen species with IL-15 and reduced glycolysis. Taken together, these data suggest that the metabolic state conferred by IL-15 inhibits T-cell apoptosis in part by maintaining low levels of active caspase-3 via S-nitrosylation.

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Nitric oxide protects cultured rheumatoid synovial cells from Fas‐induced apoptosis by inhibiting caspase‐3

Cited by 37 publications

References 32 publications

Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis

Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis

Protein oxidation markers in the serum and synovial fluid of psoriatic arthritis patients

IL-15 maintains T-cell survival via S-nitrosylation-mediated inhibition of caspase-3

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