Activation Profile of Intracellular Mitogen-Activated Protein Kinases in Peripheral Lymphocytes of Patients with Systemic Lupus Erythematosus
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...
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Published in | Journal of clinical immunology Vol. 29; no. 6; pp. 738 - 746 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Boston : Springer US
01.11.2009
Springer US Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | http://dx.doi.org/10.1007/s10875-009-9318-4 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0271-9142 1573-2592 |
DOI: | 10.1007/s10875-009-9318-4 |