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The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease.
PLoS One. 2014; 9(4):e93214.Plos

Abstract

PURPOSE

To explore whether IRAK1 and IRAK4 are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

METHODS

Thirty-nine VKH patients and thirty-two healthy controls were included in this study. The mRNA levels of IRAK1 and IRAK4 from active VKH patients, inactive VKH patients, and normal controls in peripheral blood mononuclear cells (PBMCs) were detected using real-time quantitative PCR. CD4(+)T cells were purified from PBMCs obtained from active VKH patients and normal controls. The effect of IRAK1/4 inhibition on CD4(+)T cell proliferation following stimulation with IL-18 or IL-1β was measured using a modified MTT assay. CD4(+)T cell expression of IFN-γ and IL-17 were detected by flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA). The effect of IRAK1/4 inhibition on NF-κB, STAT1, and STAT3 activation was detected by FCM.

RESULTS

The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active VKH patients compared to inactive VKH patients and healthy controls. No difference in the IRAK1 or IRAK4 mRNA level could be detected between inactive patients and healthy controls. After incubation with IRAK1/4 inhibitor, the proliferation of CD4(+)T cells was inhibited both in the active VKH patients and in the healthy controls. IRAK1/4 inhibition was also associated with a decreased expression of IFN-γ and IL-17. Phosphorylation of NF-κB, STAT1, and STAT3 in CD4(+)T from healthy controls was significantly decreased after inhibition of IRAK1/4.

CONCLUSIONS

High mRNA levels of IRAK1 and IRAK4 correlated with VKH disease activity. IRAK1 and IRAK4 play a role in the activation and proliferation of CD4(+)T cells and the higher expression observed in VKH may contribute to the pathogenesis of this blinding condition.

Authors+Show Affiliations

Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Third Military Medical University, Chongqing, P.R. China; The First Affiliated Hospital, Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.The First Affiliated Hospital, Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.The First Affiliated Hospital, Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.The First Affiliated Hospital, Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Third Military Medical University, Chongqing, P.R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24690905

Citation

Sun, Min, et al. "The Role of Interleukin-1 Receptor-associated Kinases in Vogt-Koyanagi-Harada Disease." PloS One, vol. 9, no. 4, 2014, pp. e93214.
Sun M, Yang P, Du L, et al. The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease. PLoS ONE. 2014;9(4):e93214.
Sun, M., Yang, P., Du, L., Yang, Y., & Ye, J. (2014). The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease. PloS One, 9(4), e93214. https://doi.org/10.1371/journal.pone.0093214
Sun M, et al. The Role of Interleukin-1 Receptor-associated Kinases in Vogt-Koyanagi-Harada Disease. PLoS ONE. 2014;9(4):e93214. PubMed PMID: 24690905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease. AU - Sun,Min, AU - Yang,Peizeng, AU - Du,Liping, AU - Yang,Yan, AU - Ye,Jian, Y1 - 2014/04/01/ PY - 2013/12/03/received PY - 2014/03/03/accepted PY - 2014/4/3/entrez PY - 2014/4/3/pubmed PY - 2015/12/19/medline SP - e93214 EP - e93214 JF - PloS one JO - PLoS ONE VL - 9 IS - 4 N2 - PURPOSE: To explore whether IRAK1 and IRAK4 are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS: Thirty-nine VKH patients and thirty-two healthy controls were included in this study. The mRNA levels of IRAK1 and IRAK4 from active VKH patients, inactive VKH patients, and normal controls in peripheral blood mononuclear cells (PBMCs) were detected using real-time quantitative PCR. CD4(+)T cells were purified from PBMCs obtained from active VKH patients and normal controls. The effect of IRAK1/4 inhibition on CD4(+)T cell proliferation following stimulation with IL-18 or IL-1β was measured using a modified MTT assay. CD4(+)T cell expression of IFN-γ and IL-17 were detected by flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA). The effect of IRAK1/4 inhibition on NF-κB, STAT1, and STAT3 activation was detected by FCM. RESULTS: The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active VKH patients compared to inactive VKH patients and healthy controls. No difference in the IRAK1 or IRAK4 mRNA level could be detected between inactive patients and healthy controls. After incubation with IRAK1/4 inhibitor, the proliferation of CD4(+)T cells was inhibited both in the active VKH patients and in the healthy controls. IRAK1/4 inhibition was also associated with a decreased expression of IFN-γ and IL-17. Phosphorylation of NF-κB, STAT1, and STAT3 in CD4(+)T from healthy controls was significantly decreased after inhibition of IRAK1/4. CONCLUSIONS: High mRNA levels of IRAK1 and IRAK4 correlated with VKH disease activity. IRAK1 and IRAK4 play a role in the activation and proliferation of CD4(+)T cells and the higher expression observed in VKH may contribute to the pathogenesis of this blinding condition. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24690905/The_role_of_interleukin_1_receptor_associated_kinases_in_Vogt_Koyanagi_Harada_disease_ L2 - http://dx.plos.org/10.1371/journal.pone.0093214 DB - PRIME DP - Unbound Medicine ER -