Pharmacological efficacy of anti-IL-1β scFv, Fab and full-length antibodies in treatment of rheumatoid arthritis

Qi, Jianying; Ye, Xianlong; Ren, Guangxin; Kan, Fangming; Zhang, Yunlong; Guo, Ming; Zhang, Zhiyi; Li, Deshan

doi:10.1016/j.molimm.2013.08.002

Cited by 21 publications

(15 citation statements)

References 37 publications

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“…Adenosine triphosphate (ATP), released from dying cells, has a high concentration within the cell. Extracellular ATP, one of the DAMPs, serves as the second signal for NLRP3 inflammasome activation (11 (13,14). Importantly, IL-1β maturation requires 2 steps: first, the upregulation of the precursor of IL-1β (pro IL-1β) transcription through Toll-like receptor (TLR) ligands, such as LPS; and second, the activation of the cysteine protease, caspase-1 (15).…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide/adenosine triphosphate induces IL-1β and IL-18 secretion through the NLRP3 inflammasome in RAW264.7 murine macrophage cells

Xie

Shen

Zhong

et al. 2014

International Journal of Molecular Medicine

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Abstract. The NOD-like receptor family, pyrin domaincontaining 3 (NLRP3) inflammasome plays pivotal roles in inflammation and autoimmunity. The NLRP3 inflammasome is activated in response to various signals, including pathogenassociated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). However, its role in inflammation remains unclear. In this study, we used lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to simulate an inflammatory environment as the testing model. We found that the exposure of RAW264.7 cells to LPS/ATP triggered the activation of caspase-1 (P<0.01) and the cleavage of interleukin (IL)-1β (P<0.01), as well as the release of other cytokines, such as IL-18 (P<0.01) and IL-33 (P<0.01). Extracellular potassium chloride at a high concentration (150 mM) abrogated the secretion of IL-1β and IL-18 (P<0.01), but did not reduce the processing of IL-33 (P>0.05). In addition, the silencing of NLRP3 with small interfering RNA (siRNA) suppressed the generation of proinflammatory cytokines, such as IL-1β (P<0.01), IL-18 (P<0.01), but not IL-33 (P>0.05), along with the decreased mRNA and protein expression of NLRP3 and caspase-1 (P<0.05). However, extracellular potassium at a high concentration and NLRP3 siRNA did not affect the level of apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC; P>0.05). Our results suggest that the NLRP3/ASC/caspase-1 axis participates in the regulation of pro-imflammatory cytokine secretion in RAW264.7 cells, particularly the generation of IL-1β and IL-18.

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Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide/adenosine triphosphate induces IL-1β and IL-18 secretion through the NLRP3 inflammasome in RAW264.7 murine macrophage cells

Xie

Shen

Zhong

et al. 2014

International Journal of Molecular Medicine

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“…The results of the present study indicate that miR-155 levels are positively correlated with inflammatory cytokine release (IL-1β, IL-6 and TNF-α) by synovial tissue of RA patients. It has been reported that treatment with an IL-1β antibody may significantly alleviate RA symptoms (33). An additional study indicated that inhibition of IL-1 secretion is a possible method for the treatment of RA (34).…”

Section: Discussionmentioning

confidence: 99%

miR‑155 promotes fibroblast‑like synoviocyte proliferation and inflammatory cytokine secretion in rheumatoid arthritis by targeting FOXO3a

et al. 2019

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The present study aimed to explore the expression and effects of microRNA (miR)-155 in synovial fibroblasts of patients with rheumatoid arthritis (RA). A total of 89 synovial tissues from RA patients and 49 control synovial tissues were collected, and the levels of miR-155 were measured by reverse transcription quantitative-PCR and western blotting. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues from the control group and were used to evaluate the roles of miR-155 and forkhead box protein O3a (FOXO3a). MTT assay was used to measure the proliferation of FLS. The expression of miR-155 in RA synovial tissues was significantly higher than that in the control group, but the expression of FOXO3a was significantly lower. In RA synovial tissues, miR-155 expression was negatively correlated with FOXO3a expression, but was positively correlated with the release of inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). A dual-luciferase reporter system showed that miR-155 inhibited the expression of FOXO3a in FLS cells. miR-155 also promoted secretion of the inflammatory cytokines IL-1β, IL-6 and TNF-α by FLS and proliferation of these cells by targeting FOXO3a.

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“…However, a significant disadvantage is that phage display technology can-not construct full-length antibodies [26], but only antibody fragments (including Fab and scFv) that must be further transformed into whole IgG molecules to perform functions. Several disadvantages of antibody fragments remains to be further studied and resolved, such as the low absolute tissue uptake of Fab and the high degradation of scFv by proteases [27, 28]. In comparison, full-length IgG antibodies provide substantial benefits, such as increasing half-life in the circulation system, stimulating the complement system and engaging Fc receptor-mediated effector functions [29].…”

Section: Discussionmentioning

confidence: 99%

A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway

Yuan

Wang²,

Zhang

et al. 2016

Oncotarget

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Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL). Then, the influence of LMP1-IgG on the JAK/STAT signaling pathway was investigated. The results showed that the successfully constructed LMP1-IgG inhibited proliferation, induced apoptosis, and activated ADCC and CDC of ENKTL in a concentration- and time- dependent manner. Moreover, phosphorylation of JAK3 and STAT3 was inhibited by LMP1-IgG. Our data indicate that LMP1-IgG may provide a novel and promising therapeutic strategy for the treatment of LMP1-positive ENKTL.

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Pharmacological efficacy of anti-IL-1β scFv, Fab and full-length antibodies in treatment of rheumatoid arthritis

Cited by 21 publications

References 37 publications

Lipopolysaccharide/adenosine triphosphate induces IL-1β and IL-18 secretion through the NLRP3 inflammasome in RAW264.7 murine macrophage cells

Lipopolysaccharide/adenosine triphosphate induces IL-1β and IL-18 secretion through the NLRP3 inflammasome in RAW264.7 murine macrophage cells

miR‑155 promotes fibroblast‑like synoviocyte proliferation and inflammatory cytokine secretion in rheumatoid arthritis by targeting FOXO3a

A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway

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