Host response to injury and infection is accompanied by a rapid rise of acute-phase proteins in the blood. Serum amyloid A (SAA) is a major acute-phase protein, and has been used as a marker for inflammatory diseases. However, its precise role in inflammation has not been defined. In our previous studies, we found that SAA can induce IL-8 and TNF-a secretion from peripheral blood neutrophils, and can be an endogenous ligand that induces the expression of interleukin-23 (IL-23), a hetero-dimeric cytokine that promotes autoimmune inflammation. SAA is found in very high levels in the arthritic joints of patients, along with a high concentration of certain subsets of T lymphocytes, notably helper T cell type 1 (Th1). In this study, we discovered that SAA can also stimulate CD4+ T cells to produce the cytokine interferon gamma (IFNg) and interleukin-2 (IL-2), and induce Th1 cell differentiation and proliferation. Our data showed that SAA-induced IL-2 production and cell proliferation can be blocked by the inhibitor of MAP kinase p38, and the phosphorylation of p38 indeed can be increased after SAA stimulation. These results suggest that SAA, which is found in arthritic joints, may play a role to induce Th1 cell production, and is perhaps a missing link in our understanding of Rheumatoid Arthritis.
- Copyright © 2013 by The American Association of Immunologists, Inc.