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Lymphocyte α-kinase is a gout-susceptible gene involved in monosodium urate monohydrate-induced inflammatory responses

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Abstract

The molecular functions and pathophysiologic role of the lymphocyte α-kinase gene (ALPK1) in gout are unknown. We aimed to examine ALPK1 expression in patients with gout and investigate its role in monosodium urate monohydrate (MSU)-induced inflammatory responses. Microarray data mining was performed with six datasets containing three clinical gout and three volunteer samples. Real-time quantitative polymerase chain reaction (qPCR) assay was used to profile ALPK1 mRNA expression in 62 independent samples. RNA interference for ALPK1 suppression in THP1 cells (human monocytic cell line) was used to scrutinize the functional role of ALPK1 in MSU-mediated inflammatory responses, and ALPK1 expression in MSU-treated THP1 cells was determined by qPCR and Western blot analysis. Cytokine mRNA expression in HEK293 cells after incubation with different concentrations of MSU crystals in the presence or absence of ALPK1 was also detected by qPCR, and ERK1/2, p38, and JNK expressions were investigated by Western blot analysis. ALPK1 mRNA was overexpressed in the clinical gout samples. MSU treatment promoted ALPK1 expression at the mRNA and protein levels. Furthermore, ALPK1 knockdown in THP1 cells resulted in a markedly decreased IL-1β, TNF-α, and IL-8 mRNA expression; plasmid ALPK1 transfection and MSU stimulation synergistically increased the mRNA expression of these cytokines in a concentration-dependent manner. The synergistic effect also led to ERK1/2 activation. ALPK1 is a gout-susceptible gene involved in MSU-induced inflammatory responses. It may contribute to the development of gout by enhancing the inflammatory responses via the mitogen-activated protein kinase pathway.

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Acknowledgments

This study was supported by grants from Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Ministry of Education, Taiwan (KMU-EM-98-1-1 and KMU-EM-99-1-1), and the National Science Council, Taiwan (NSC97-2314-B-037-007-MY3 and NSC99-2628-B-037-039-MY3).

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shu-Jung Wang, Yi-Shan Tsai & Ying-Chin Ko

  2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Pin Tu, Shang-Lun Chiang & Chi-Pin Lee

  3. Department of Public Health and Environmental Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Pin Tu

  4. The Leipzig School of Human Origins, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

    Albert Min-Shan Ko

  5. Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shean-Jaw Chiou

  6. Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Su-Shin Lee

  7. Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, San-Ming District, Kaohsiung, 807, Taiwan

    Ying-Chin Ko

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  1. Shu-Jung Wang
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Wang, SJ., Tu, HP., Ko, A.MS. et al. Lymphocyte α-kinase is a gout-susceptible gene involved in monosodium urate monohydrate-induced inflammatory responses. J Mol Med 89, 1241–1251 (2011). https://doi.org/10.1007/s00109-011-0796-5

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  • DOI: https://doi.org/10.1007/s00109-011-0796-5

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