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Molecules 2015, 20(10), 19588-19604; doi:10.3390/molecules201019588

Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus

1
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China
2
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China
3
State Key Laboratory of Phytochemistry and Plant Resources in West China, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China
4
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China
5
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Received: 21 September 2015 / Revised: 17 October 2015 / Accepted: 21 October 2015 / Published: 27 October 2015
(This article belongs to the Section Medicinal Chemistry)
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Abstract

We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19+ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE. View Full-Text
Keywords: cytokines; IL-36; regulatory B lymphocytes; systemic lupus erythematosus cytokines; IL-36; regulatory B lymphocytes; systemic lupus erythematosus
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chu, M.; Wong, C.K.; Cai, Z.; Dong, J.; Jiao, D.; Kam, N.W.; Lam, C.W.K.; Tam, L.S. Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus. Molecules 2015, 20, 19588-19604.

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