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1.
Mediators Inflamm ; 2022: 9968847, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35095344

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and chronic inflammation. The etiology and pathogenesis of SLE are complicated in which dysfunction of CD4+ T cells is largely engaged. In this study, we investigated the manners of CD4+ T cells in antibody production in a lupus-like mouse model through peritoneal injection of pristane reagent. With the increase in total IgG/IgM and autoantibody production after 6 months, CD4+ T cells exhibited activated phenotypes with the elevated CD44, ICOS, OX40, and PD-1 expression. Pristane injection induced the increase in IgM levels in both wild-type and T cell-deficient TCRα -/- mice whereas IgG, IgG1, and IgG2a production was impaired. When adoptively transferring CD4+ T cells into T cell-deficient mice or coculturing CD4+ T cells and B cells in vitro, it was found that CD4+ T cells derived from pristane-treated mice could help the production of total IgG as well as IgG1/IgG2a in a more efficient manner both in vivo and in vitro. While MHC was dispensable for IgG production, ICAM-1 likely functioned as an attenuating factor for IgG production. Our study thus reveals that CD4+ T cells in pristane-treated mice play important roles in IgG production, which implies the critical roles in the induction of pathological autoantibodies in MHC-independent and ICAM-1-dependent manners.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T , Animais , Autoanticorpos , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Imunoglobulina G , Molécula 1 de Adesão Intercelular , Camundongos , Linfócitos T/metabolismo , Terpenos/toxicidade
2.
Zhongguo Zhong Yao Za Zhi ; 43(10): 2067-2073, 2018 May.
Artigo em Chinês | MEDLINE | ID: mdl-29933672

RESUMO

Spray drying technology was used to produce co-processed excipients mannitol- hydroxypropyl methylcellulose (HPMC), and study the scaled-up production. The consistency of powder and tablet properties before and after scale-up of co-processed excipients was compared, and their applicability in traditional Chinese medicine (TCM) powder's direct compression was tested on five TCM extracts such as gardenia extract and Radix Paeoniae Alba extract. It was shown that after scaled-up production, the key properties of co-processed excipients had little changes (such as compactability, disintegrating time, and lubrication sensitivity) or improvement (such as flowability and yield). As compared to commercially available spray-dried mannitol, co-processed excipients achieved better compactability and higher drug loading for direction compression of TCM powder. In conclusion, the mannitol-HPMC co-processed excipient, with excellent physicomechanical properties, is promising to be explored as a new excipient for direct powder compression.


Assuntos
Composição de Medicamentos , Excipientes , Derivados da Hipromelose , Manitol , Medicina Tradicional Chinesa , Tamanho da Partícula , Extratos Vegetais , Pós , Comprimidos
3.
J Mol Med (Berl) ; 90(7): 837-46, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22307521

RESUMO

Increasing evidences suggest that the type I interferon α (IFN α) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFN α 1bScFv01 and corresponding whole antibody AIFN α 1bIgG01 to human interferon α 1b (IFN α 1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFN α 1b or naïve IFN α from SLE patients' sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFN α 1bScFv01-IFN α 1b complex solved to 2.8 Å resolution revealed that both Pro26-Gln40 region in loop AB and Glu147-Arg150 region in helix E of IFN α 1b contribute to binding with AIFN α 1bScFv01. Four residues of above two regions (Leu30, Asp32, Asp35 and Arg150) are critical for the formation of antigen-antibody complexes. AIFN α 1bScFv01 shares partial epitopes of IFN α 1b with its receptor IFNAR2 but with much higher binding affinity to IFN α 1b than IFNAR2. Thus, AIFN α 1bIgG01 exhibits its neutralizing activity through competition with IFNAR2 to bind with IFN α and prevents the activation of IFN α-mediated signaling pathway. Our results highlight the potential use of the human antibody for modulating the activity of IFN α in SLE.


Assuntos
Anticorpos Monoclonais Humanizados/química , Interferon-alfa/química , Interferon-alfa/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos de Cadeia Única/química , Animais , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Afinidade de Anticorpos , Complexo Antígeno-Anticorpo/química , Modelos Animais de Doenças , Humanos , Lúpus Eritematoso Sistêmico/terapia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas/imunologia , Transdução de Sinais , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/uso terapêutico
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 27(2): 119-22, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21315035

RESUMO

AIM: To establish the systemic lupus erythematosus (SLE) mouse model through pristane intraperitoneal injection and discuss the pathogenesis of SLE in this mouse model. METHODS: Single intraperitoneal injection of 0.5 mL Pristane or PBS was applied on 6-8 week old female BALB/c mice. The percentage of IFN-α producing cells (CD11b(+);Ly6C(high);)and B cells and the expression of B cell activation surface marker(Aß1(d);)in peripheral blood were detected by flow cytometry every 2 weeks. Serum total IgG and auto-antibodies (anti-dsDNA, anti-sm RNP, anti-ribosomal P0)were detected by ELISA at different time point. The percentage of peritoneal CD11b(+);Ly6C(high);cells and Aß1(d);expression in spleen were also detected by flow cytometry after 6 months. glomerular IgG deposition and kidney histopathologic changes were determined by direct immunofluorescence and H&E staining respectively. RESULTS: Total IgG began to increase since 2 months after the pristane injection, while auto-antibodies were detected after 3 moths, both of which peaked after 6 moths and maintained the high level. Most of the pristane treated mice developed arthritis, glomerular immune complex deposition and kidney damage. The percentage of peripheral and peritoneal IFN-α producing cells was much higher in pristane group than that of the PBS control group since 2 weeks after intraperitoneal injection. The mean fluorescence intensity (MFI) of B cell activation marker(Aß1(d);) in pristane group was also higher than PBS group in both peripheral blood and spleen indicating B cell over activation. CONCLUSION: Intraperitoneal injection of pristane can successfully establish a SLE mouse model which may be used in research of the SLE pathogenesis. Increased percentage of IFN-αproducing cells may play an etiopathogenic role in abnormal B cell activation and SLE development in this model.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Terpenos , Animais , Complexo Antígeno-Anticorpo/imunologia , Artrite/imunologia , Artrite/patologia , Autoanticorpos/sangue , Linfócitos B/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina G/sangue , Imunossupressores , Interferon-alfa/metabolismo , Rim/imunologia , Rim/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/patologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Baço/metabolismo
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