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

• Published in: Journal of clinical immunology Vol. 29; no. 6; pp. 738 - 746
• Main Authors: Wong, Chun K, Wong, Purple T. Y, Tam, L. S, Li, Edmund K, Chen, D. P, Lam, Christopher W. K
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.11.2009; Springer US; Springer Nature B.V
• Subjects: Adult; Aged; B-Lymphocytes; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; CD8-Positive T-Lymphocytes; Female; Humans; Immunology; Infectious Diseases; Internal Medicine; JNK Mitogen-Activated Protein Kinases - metabolism; Lupus Erythematosus, Systemic - immunology; Lymphocytes - immunology; Medical Microbiology; Middle Aged; Mitogen-Activated Protein Kinase 3 - metabolism; Mitogen-Activated Protein Kinases - immunology; Mitogen-Activated Protein Kinases - metabolism; Monocytes; p38 Mitogen-Activated Protein Kinases - metabolism; T-Lymphocytes, Helper-Inducer; Young Adult; CXCL10; lymphocytes; IL-18; mitogen-activated protein kinases; systematic lupus erythematosus
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-009-9318-4

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.