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Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts

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Cellular & Molecular Immunology 2022年第10期19卷 1185-1195页

作者： Ruby J.Siegel Anil K.singh Paul M.Panipinto Farheen S.Shaikh Judy Vinh Sang U.han H.Mark Kenney Edward M.Schwarz Cynthia S.Crowson Sadik A.Khuder Basil S.Khuder David A.Fox Salahuddin Ahmed Department of Pharmaceutical Sciences Washington State University College of Pharmacy and Pharmaceutical SciencesSpokaneWAUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNYUSA Department of Quantitative Health Sciences and Division of Rheumatology Mayo ClinicRochesterMNUSA Department of Medicine and Public Health University of ToledoToledoOHUSA Department of Pathology and Laboratory Medicine Phoenix Children’s HospitalPhoenixAZUSA Department of Medicine Division of Rheumatology and Clinical Autoimmunity Center of ExcellenceUniversity of Michigan Medical SystemAnn ArborMIUSA Division of Rheumatology University of Washington School of MedicineSeattleWAUSA

Extracellular sulfatase-2(Sulf-2)influences receptor-ligand binding and subsequent signaling by chemokines and growth factors,yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis(RA).In the present study,we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts(RASFs).Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg *** sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated~2500 genes compared to scrambled *** Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in *** blot,ELISA,and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1,VCAM1,CAD11,PDPN,CCL5,CX3CL1,CXCL10,and *** studies identified the protein kinase C-delta(PKCδ)and c-Jun N-terminal kinase(JNK)pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and *** of Sulf-2 abrogated TNF-α-induced RASF ***-2 knockdown with siRNA and inhibition by OKN-007 suppressed the TNF-α-induced phosphorylation of PKCδand JNK,thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human ***,Sulf-2 expression positively correlated with the expression of TNF receptor 1,and coimmunoprecipitation assays demonstrated the binding of these two proteins,suggesting they exhibit crosstalk in TNF-α*** study identified a novel role of Sulf-2 in TNF-αsignaling and the activation of RA synoviocytes,providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA.

关键词： Sulfatase-2 TNF-α Rheumatoid arthritis Synovial fibroblasts Signal transduction

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Effect of Storage Temperature on Sensory and Physicochemical Properties of Wheat Flour Fortified with Elevated Levels of Vitamin A in Combination with Three Types of Iron

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Journal of Agricultural Science and Technology(A) 2014年第7期4卷 563-575页

作者： Philip G. Crandall han-Seok Seo Robert Pellegrino Corliss A. O'Bryan Jean F. Meullenet Navam S.Hettiarachchy Anna M. Washburn gur S. Ranhotra Department of Food Science University of Arkansas Fayetteville 72704 AR USA SFC Fluidics LLC Fayetteville 72 701 AR USA AIB International Manhattan 66502 KS USA

Many persons worldwide are deficient in micronutrients, two of the most common being vitamin A and iron. Fortification of staple food is a commonly used and effective method of boosting micronutrient intake. Wheat flour is widely used around the world and makes a good vehicle for fortification, but there is a lack of studies on the storage stability of fortified wheat flour. In this study, we fortified wheat flour with elevated levels of vitamin A and three sources of iron and stored it for up to 16 weeks at refrigerated or room temperature or elevated temperature. The rate of disappearance of vitamin A was monitored by high pressure liquid chromatography, and the rate of disappearance was found to be directly proportional to the duration of storage and storage temperature. Higher temperatures contributed to greater loss of vitamin A. Iron, regardless of source, did not play a major role in contributing to the rate of vitamin A loss. Flour functionality was assessed by baking loaves of bread from the stored flour and assessing physical properties as well as subjecting the loaves to an expert sensory panel. Functionality also changed with time and temperature of storage, but sensory analysis found that these changes were not detrimental to the quality of bread baked from the stored flours. Trained sensory panelists found that breads baked from flours fortified with ferrous sulfate and stored at the three temperatures for times up to eight weeks were markedly different from fortified flours using hydrogen reduced irons.

关键词：营养强化剂维生素A 贮藏温度硫酸亚铁小麦粉理化性质储存稳定性强化面粉

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