| Adhesion molecules are vital in cell-cell and cell-extracellular matrix interactions. The regulation of adhesion molecule expression and activity plays a critical role in the physiology of many immunological events under both physiological and pathophysiological conditions. Among the many adhesion proteins, the CD44 family of cell adhesion glycoproteins, is an important mediator in events such as tumorigenesis and metastasis, cell migration, angiogenesis, wound healing, and inflammatory responses. The regulation of CD44 expression as well as activation of binding to its ligand, hyaluronan (HA), are tightly regulated phenomena. The molecular mechanisms and cell signaling events behind the regulation of CD44 expression and HA binding events are not well understood. In this study, I examined the regulation of CD44 expression and HA binding in two models systems: human monocytic cells and human B cells.; LPS, a bacterial cell wall component, regulates CD44 expression and may modulate CD44-mediated biological effects in monocytic cells during inflammation and immune responses. In this study, I show that in normal human monocytes, LPS and LPS-induced cytokines IL-10 and TNF-α enhance CD44 expression. To delineate the mechanism underlying LPS-induced CD44 expression, I investigated the role of mitogen-activated protein kinases (MAPK), p38, p42/44 extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) by employing specific inhibitors. I demonstrate the partial involvement of p38 MAPK in TNF-α-induced CD44 expression in both monocytes and the promonocytic THP-1 cell line. However, neither p38 nor p42/44 MAPKs were involved in IL-10-induced CD44 expression in monocytes. (Abstract shortened by UMI.)... |
