Activation profile of intracellular mitogen-activated protein kinases in peripheral lymphocytes of patients with systemic lupus erythematosus.
BACKGROUND
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.


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.


CONCLUSIONS
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).


CONCLUSIONS
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.
Wong
Chun K
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Wong
Purple T Y
PT
Tam
L S
LS
Li
Edmund K
EK
Chen
D P
DP
Lam
Christopher W K
CW
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes; D006377:T-Lymphocytes, Helper-Inducer; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases