Dataset Information

Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer.

ABSTRACT: The interleukin (IL)-12 family, composed of heterodimeric cytokines including IL-12 (formed by IL-12p35 and IL-12p40 subunits), IL-23 (formed by IL-23p19 and IL-12p40 subunits), IL-27 (formed by IL-27p28 and EBI3 subunits) and IL-35 (formed by IL-12p35 and EBI3 subunits), establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines to tumors. However, the role of IL-12 family in breast cancer (BC) progression and prognosis remains unclear. In the present study, we demonstrated evidence indicating that EBI3, IL-12p35 and IL-12p40 but not IL-23p19 or IL-27p28 were highly expressed in BC tissues, suggested that tumor derived EBI3, IL-12p35 and IL-12p40 were associated with tumor progression. Circulating IL-12 and IL-23 low expressed, but IL-27 and IL-35 high expressed in BC patients, especially circulating IL-23 associated with IL-35 to mediate BC tumor resection. Ki-67, p53 and EGFR expression on BC tissues, as well as CA125, CA153 and CA199 levels on BC bloods increased when circulating IL-23: IL-35 ratio decreased. Together, for the first time, our data suggest that circulating IL-23: IL-35 ratio may be an important indicator association with BC progression and prognosis. However, further research should be carried out to assess the implications of circulating IL-23: IL-35 ratio in a larger sample size.

SUBMITTER: Chen G

PROVIDER: S-EPMC4891437 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer.

Chen Guanghui G Liang Yanfang Y Guan Xin X Chen Hui H Liu Qiankun Q Lin Bihua B Chen Can C Huang Mingyuan M Chen Jianan J Wu Weiquan W Liang Yi Y Zhou Keyuan K Zeng Jincheng J

American journal of translational research 20160515 5

The interleukin (IL)-12 family, composed of heterodimeric cytokines including IL-12 (formed by IL-12p35 and IL-12p40 subunits), IL-23 (formed by IL-23p19 and IL-12p40 subunits), IL-27 (formed by IL-27p28 and EBI3 subunits) and IL-35 (formed by IL-12p35 and EBI3 subunits), establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines to tumors. However, the role of IL-12 family in breast cancer (BC) progression and prognosis remains unclear. I ...[more]

PMID: 27347332

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Project description:Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

Project description:Objective: To investigate the relationship of interleukin (IL)-35 with sarcoidosis. Methods: We enrolled 114 inpatients and outpatients with sarcoidosis at the Shanghai Pulmonary Hospital, and 24 healthy controls between March 2015 and December 2017. Serum and whole blood were collected during the follow-up period. Serum IL-35 levels were detected by ELISA. Proportions of Breg, Tfh, and Treg cells in the peripheral blood were detected using flow cytometry (FCM). The mRNA levels of p35, EBI3, and GAPDH in CD19+ cells and CD4+ cells were detected by real-time PCR. Sarcoidosis granuloma mice models were established with Propionibacterium acnes (PA) and one group was treated with IL-35 antibodies. Proportions of Breg, Tfh, and Treg cells in the peripheral blood and bronchoalveolar lavage fluid (BALF) were detected by FCM. Results: The IL-35 levels and the proportions of Breg and Tfh cells in the peripheral blood of patients with active sarcoidosis were significantly higher compared to patients with stable sarcoidosis and healthy controls. Moreover, the IL-35 level in patients with progressive disease was lower than that found at the initial visit. EBI3 and p35 mRNA levels in CD19+ cells for patients with active sarcoidosis were significantly higher as compared to patients with stable sarcoidosis and healthy controls, while there were no significant differences in p35 and EBI3 mRNA levels in CD4+ cells between the three groups. In the mouse model of sarcoidosis, there were loose granulomata (macrophage accumulation in the bronchial areas and immature granuloma) after intervention with IL-35 antibodies. Meanwhile, the proportions of Breg cells in the peripheral blood and BALF of the model were significantly increased, while the proportion of Treg cells declined significantly. After intervention with IL-35 antibodies, the proportion of Breg cells in the peripheral blood of mice decreased significantly as compared to the mice not exposed to anti-IL-35 antibodies. Conclusion: IL-35 levels increased significantly in the serum of patients with active sarcoidosis, and lower IL-35 levels were correlated with persistent disease. Serum IL-35 levels might be better correlated with Breg cell functions.

Dataset Information

Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer.

Publications

Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer.

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