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Activation Profile of Intracellular Mitogen-Activated Protein Kinases in Peripheral Lymphocytes of Patients with Systemic Lupus Erythematosus

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Abstract

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes. Abnormal activation of intracellular signaling molecules in lymphocytes by inflammatory cytokines can instigate the inflammation in SLE.

Materials and Methods

The activation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in inflammatory cytokine IL-18-activated monocytes, CD4+ T helper (Th) lymphocytes, CD8+ T lymphocytes, and CD19+B lymphocytes in 22 SLE patients and 20 sex- and age-matched control subjects were measured by flow cytometry.

Results and Discussion

The basal expressions of phospho-p38 MAPK in CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes were significantly higher in SLE patients than controls (all p < 0.05). The expression of phospho-p38 MAPK in CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes, and phospho-JNK in CD8+ T lymphocytes and B lymphocytes was also significantly elevated in SLE patients upon the activation by IL-18, exhibiting significant correlation with the plasma concentrations of Th1 chemokine CXCL10 (all p < 0.05). The expression of phospho-JNK in IL-18 activated CD8+ T lymphocytes and the relative % fold increase of the expression of phospho-JNK upon IL-18 activation in B lymphocytes were significantly correlated with SLE disease activity index (both p < 0.05).

Conclusion

The inflammation-mediated activation of JNK and p38 MAPK signaling pathways in T and B lymphocytes can be the underlying intracellular mechanisms causing lymphocyte hyperactivity in SLE.

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Acknowledgment

The study was supported by a Direct Grant for Research (2041272), The Chinese University of Hong Kong.

Conflict of interest

No conflict of interest has been declared by the authors.

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Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China

    Chun K. Wong, Purple T. Y. Wong, D. P. Chen & Christopher W. K. Lam

  2. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China

    L. S. Tam & Edmund K. Li

  3. Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China

    Christopher W. K. Lam

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  1. Chun K. Wong
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  2. Purple T. Y. Wong
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  3. L. S. Tam
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  6. Christopher W. K. Lam
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Correspondence to Christopher W. K. Lam.

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Wong, C.K., Wong, P.T.Y., Tam, L.S. et al. Activation Profile of Intracellular Mitogen-Activated Protein Kinases in Peripheral Lymphocytes of Patients with Systemic Lupus Erythematosus. J Clin Immunol 29, 738–746 (2009). https://doi.org/10.1007/s10875-009-9318-4

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  • DOI: https://doi.org/10.1007/s10875-009-9318-4

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