Dataset Information

Suppressors of cytokine signaling in tuberculosis.

ABSTRACT: Tuberculosis (TB), a global disease mainly infected by Mycobacterium tuberculosis, remains leading public health problem worldwide. Suppressors of cytokine signaling (SOCSs) play important roles in the protection against microbial infection. However, the relationship between members of the SOCS family and tuberculosis infection remains unclear. Using peripheral blood mononuclear cells, we investigated the mRNA expression profiles of SOCS subfamilies among active TB, latent tuberculosis infection (LTBI), and healthy individuals. Our results showed that active tuberculosis subjects had higher levels of SOCS-3 mRNA, lower expressions of SOCS-2, -4, -5, -6, -7, and cytokine-inducible SH2-containing protein-1 (CIS-1) mRNAs, but not SOCS-1 mRNA than healthy and LTBI subjects. In men, LTBI patients had lower SOCS-3 than healthy subjects, and active TB patients had lower levels of SOCS-4, -5, and CIS-1 mRNAs but higher levels of SOCS-3 mRNA than healthy subjects. In women, LTBI patients had lower SOCS-3 mRNA level than healthy subjects, and active TB patients had lower CIS-1 mRNA level than healthy subjects. In non-aged adults (< 65 years old), TB patients had higher SOCS-3 mRNA and lower levels of SOCS-2, -4, -5, -6, -7, and CIS-1 mRNAs; whereas, aged TB patients (? 65 years old) had lower levels of SOCS-5 and CIS-1 mRNAs. These data suggest that particular SOCS members and their correlative relationships allow discrimination of active TB from healthy and LTBI subjects.

SUBMITTER: Lee SW

PROVIDER: S-EPMC5400265 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Suppressors of cytokine signaling in tuberculosis.

Lee Shih-Wei SW Liu Chi-Wei CW Hu Jia-Ying JY Chiang Li-Mei LM Chuu Chih-Pin CP Wu Lawrence Shih-Hsin LS Kao Yung-Hsi YH

PloS one 20170421 4

Tuberculosis (TB), a global disease mainly infected by Mycobacterium tuberculosis, remains leading public health problem worldwide. Suppressors of cytokine signaling (SOCSs) play important roles in the protection against microbial infection. However, the relationship between members of the SOCS family and tuberculosis infection remains unclear. Using peripheral blood mononuclear cells, we investigated the mRNA expression profiles of SOCS subfamilies among active TB, latent tuberculosis infection ...[more]

PMID: 28430824

Similar Datasets

Project description:ObjectivesSuppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling that function via the JAK/STAT pathway (Janus kinase/signal transducers and activators of transcription). Eight SOCS proteins, SOCS1-SOCS7 and CIS-1 (cytokine-inducible SH2-domain, with similar structure to the other SOCS proteins) have been identified, of which SOCS1, 2, and 3 and CIS-1 are the best characterised. A characteristic feature of osteoarthritis (OA) is increased production by articular chondrocytes of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα), which may be induced by mechanotransduction and contribute to cartilage destruction. In this study, we have compared the gene expression of SOCS1, 2, 3 and CIS-1 in healthy and OA human chondrocytes, and also analyzed the effects of IL-1β and TNFα on the levels of mRNA encoding these SOCS family members. In addition, SOCS2 protein production was assessed and the CpG methylation status of the SOCS2 promoter was analyzed to determine the role of epigenetics in its regulation.MethodsFemoral heads were obtained after joint replacement surgery for late stage OA and hemiarthroplasty following a fracture of the neck of femur (#NOF). Chondrocytes from the superficial layer of OA cartilage and the deep zone of #NOF cartilage were isolated by sequential treatment with trypsin, hyaluronidase and collagenase B. Total DNA and RNA were extracted from the same chondrocytes, and the levels of SOCS1, 2, 3 and CIS-1 mRNA were determined by qRT-PCR. The percentage of methylation in the CpG sites of the SOCS2 proximal promoter was quantified by pyrosequencing. Alternatively, healthy chondrocytes were isolated from #NOF cartilage and cultured with and without a mixture of IL-1β and oncostatin M (OSM, both 2.5ng/ml) or TNFα (10ng/ml). The short-term cultures with single cytokine treatment were harvested 24 and 72h after treatment, and the long-term cultures were maintained for 4-5 weeks until confluent with periodical cytokine stimulation. Total RNA was extracted and mRNA levels were determined by qRT-PCR.ResultsThe SOCS2 and CIS-1 mRNA levels were reduced by approximately 10-fold in OA samples compared to control samples, while SOCS1 and SOCS3 showed similar expression patterns in OA and control chondrocytes. The SOCS2 and CIS-1 mRNA levels declined by 6-fold and 3-fold with long-term treatment with IL-1β and OSM in combination and TNFα, respectively. There was no significant difference in the CpG methylation status of the SOCS2 promoter between healthy and OA chondrocytes. Similarly, cytokine stimulation did not change the CpG methylation status of the SOCS2 promoter.ConclusionsThis study demonstrates the reduced expression of SOCS2 and CIS-1 in OA, while SOCS1 and SOCS3 were unaffected. The observation that long-term treatment with inflammatory cytokines attenuated the expression of SOCS2 and CIS-1 suggests a potential positive feedback mechanism, and a role of SOCS in the pathology of OA.

Dataset Information

Suppressors of cytokine signaling in tuberculosis.

Publications

Suppressors of cytokine signaling in tuberculosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure