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Changes in toll-like receptor (TLR)4–NFκB–IL1β signaling in male gout patients might be involved in the pathogenesis of primary gouty arthritis

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Abstract

We undertook this study to determine whether the altered toll-like receptor (TLR)4-nuclear factor κB (NFκB)-interleukin1β (IL1β) signaling in peripheral blood of gout patients could provide insights into the pathogenesis of primary gouty arthritis (GA). TLR4 mRNA, TLR4 and NFκBp65 proteins expression and IL1β production were measured in 52 acute GA (AGA) and 34 non-acute GA (NAGA) male patients and 78 male healthy subjects (HC). NFκBp65 transcriptional activity and IL1β production were measured after TLR4 inhibition with anti-TLR4 antibody in peripheral whole blood from 13 AGA patients. The TLR4, NFκBp65 and IL1β expression was significantly increased in the AGA group than those in the NAGA or HC group (P < 0.05, respectively), also the levels were higher in the NAGA group comparing with those in the HC group (P < 0.05, respectively). Furthermore, moderate positive correlations were observed between concentration of uric acid and the TLR4 mRNA level, serum IL1β production (r = 0.649, 0.616), and strong positive correlation was observed between TLR4 mRNA level and serum IL1β (r = 0.848) in 52 AGA patients. On the other hand, NFκBp65 level and IL1β production were dramatically reduced after TLR4 blockade with anti-TLR4 antibody in peripheral blood from the AGA patients (P < 0.05, respectively). TLR4–NFκB–IL1β signaling might play a crucial role in the development of acute inflammation in primary gout patients.

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Acknowledgments

This work was partly supported by Natural Science Foundation of China (81272047) and Key Program, Science and Technology Bureau of Sichuan (2012SZ0171).

Conflict of interest

All the authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Institute of Rheumatology and Immunology, Department of Rheumatology and Hematology, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong, 637000, Sichuan, China

    Yu-Feng Qing, Jing-Guo Zhou & Li Jiang

  2. Department of Geriatrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong, 637007, Sichuan, China

    Quan-Bo Zhang

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  1. Yu-Feng Qing
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Correspondence to Jing-Guo Zhou.

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Qing, YF., Zhang, QB., Zhou, JG. et al. Changes in toll-like receptor (TLR)4–NFκB–IL1β signaling in male gout patients might be involved in the pathogenesis of primary gouty arthritis. Rheumatol Int 34, 213–220 (2014). https://doi.org/10.1007/s00296-013-2856-3

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  • DOI: https://doi.org/10.1007/s00296-013-2856-3

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