Functional proteomics revealed IL-1β amplifies TNF downstream protein signals in human synoviocytes in a TNF-independent manner

Shen, Shuai; Guo, Jiahui; Luo, Yanzhang; Zhang, Wanling; Cui, Yizhi; Wang, Qing; Zhang, Zhiguang; Wang, Tong

doi:10.1016/j.bbrc.2014.06.008

Cited by 29 publications

(43 citation statements)

References 32 publications

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“…The loss of chondrocyte function and proinflammatory cytokines, such as IL-6, IL-8, IL-1 β , and TNF-alpha, play crucial roles in the initiation and progression of OA, and thus the inhibition of these factors is an important issue for the treatment of OA [22, 23]. In this study, we found that SOCS1 silencing regulates apoptosis and inflammatory cytokine production in human osteoarthritic chondrocytes, probably by activating IL-4 signaling.…”

Section: Discussionmentioning

confidence: 99%

SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes

Sun²,

Lei

et al. 2017

BioMed Research International

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Recently, Suppressor of Cytokine Signaling 1 (SOCS1) was identified as a potential therapeutic target for osteoarthritis (OA) treatment. However, the mechanisms and signaling pathways of SOCS1 in the regulation of OA development are unclear. The purpose of the current study was to investigate whether interleukin- (IL-) 4 was involved in regulatory mechanism of SOCS1 in human osteoarthritic chondrocytes. First, IL-1β was used to stimulate human osteoarthritic chondrocytes isolated from the articular cartilage of OA patients undergoing total knee replacement. The protein and mRNA expression levels of SOCS1 were upregulated in IL-1β-stimulated human osteoarthritic chondrocytes compared with control cells. The knockdown of SOCS1 increased cell viability and inhibited cell apoptosis. It was also found that IL-4 expression was increased by SOCS1 silencing. Additionally, knockdown of IL-4 reduced cell viability and increased cell apoptosis of osteoarthritic chondrocytes transfected with SOCS1 siRNA. Moreover, the decreased expression of inflammatory factors induced by SOCS1 was enhanced by IL-4 knockdown. In conclusion, IL-4 signaling plays a crucial role in the regulatory functions of SOCS1 in apoptosis and inflammation in human osteoarthritic chondrocytes. These findings provide a potential therapeutic target for the clinical treatment of OA.

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Section: Discussionmentioning

confidence: 99%

SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes

Sun²,

Lei

et al. 2017

BioMed Research International

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“…The Upstream Analysis was used to find out upstream regulators of DEPs with activation/inhibition status predictions51.…”

Section: Methodsmentioning

confidence: 99%

“…IB was performed as we previously described464851. Antibodies used were rabbit anti-CA2 pAb (1:2000, PROTEINTECH GROUP, INC., China) and HRP-conjugated goat anti-rabbit mAb (1:2000, Bioworld).…”

Section: Methodsmentioning

confidence: 99%

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

Luo

Mok

Lin

et al. 2017

Sci Rep

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Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC.

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“…33 In brief, supernatants were collected from the untreated and drugtreated cells and mixed with the LDH substrate. The light absorbance was then measured at 490 and 630 nm.…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Finding Missing Proteins from the Epigenetically Manipulated Human Cell with Stringent Quality Criteria

et al. 2015

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The chromosome-centric human proteome project (C-HPP) has made great progress of finding protein evidence (PE) for missing proteins (PE2-4 proteins defined by the neXtProt), which now becomes an increasingly challenging field. As a majority of samples tested in this field were from adult tissues/cells, the developmental stage specific or relevant proteins could be missed due to biological source availability. We posit that epigenetic interventions may help to partially bypass such a limitation by stimulating the expression of the "silenced" genes in adult cells, leading to the increased chance of finding missing proteins. In this study, we established in vitro human cell models to modify the histone acetylation, demethylation, and methylation with near physiological conditions. With mRNA-seq analysis, we found that histone modifications resulted in overall increases of expressed genes in an even distribution manner across different chromosomes. We identified 64 PE2-4 and six PE5 proteins by MaxQuant (FDR < 1% at both protein and peptide levels) and 44 PE2-4 and 7 PE5 proteins by Mascot (FDR < 1% at peptide level) searches, respectively. However, only 24 PE2-4 and five PE5 proteins in Mascot, and 12 PE2-4 and one PE5 proteins in MaxQuant searches could, respectively, pass our stringently manual spectrum inspections. Collectively, 27 PE2-4 and five PE5 proteins were identified from the epigenetically modified cells; among them, 19 PE2-4 and three PE5 proteins passed FDR < 1% at both peptide and protein levels. Gene ontology analyses revealed that the PE2-4 proteins were significantly involved in development and spermatogenesis, although their chemical-physical features had no statistical difference from the background. In addition, we presented an example of suspicious PE5 peptide spectrum matched with unusual AA substitutions related to post-translational modification. In conclusion, the epigenetically manipulated cell models should be a useful tool for finding missing proteins in C-HPP. The mass spectrometry data have been deposited to the iProx database (accession number: IPX00020200).

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Functional proteomics revealed IL-1β amplifies TNF downstream protein signals in human synoviocytes in a TNF-independent manner

Cited by 29 publications

References 32 publications

SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes

SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

Finding Missing Proteins from the Epigenetically Manipulated Human Cell with Stringent Quality Criteria

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