Résumé
CD137, which is expressed on activated T cells, plays a critical role in inflammatory responses. However, the exact role that CD137 plays in monocytes is not fully known. Here we studied the expression and function of CD137 in human monocytic THP-1 cells, which we found constitutively expresses CD137 at the mRNA and protein level. Cross-linking of CD137 increased the secretion of IL-8 and TNF-alpha, promoted the expression of CD54 and CD11b, and increased adhesion to extracellular matrix (ECM) proteins. In particular CD137-induced adhesion of THP-1 cells was inhibited by an inhibitor of mitogen-activated protein kinase kinase (MEK), but not by a p38 kinase inhibitor. Taken together, these results show that the adhesion and cytokine production of THP-1 cells induced by CD137 occur via activation of MEK, which results in the activation of ERK-1/2 signaling pathways. Therefore, this study suggests that CD137 induces an activating and migrating signal during inflammatory processes.
Sujets)
Humains , Antigènes CD/biosynthèse , Antigènes CD11/biosynthèse , Adhérence cellulaire , Molécules d'adhérence cellulaire/biosynthèse , Lignée cellulaire , Cytokines/biosynthèse , Activation enzymatique , Protéines de la matrice extracellulaire/métabolisme , Cytométrie en flux , Immunité innée , Molécule-1 d'adhérence intercellulaire/biosynthèse , Interleukine-8/biosynthèse , Mitogen-Activated Protein Kinase 1/métabolisme , Mitogen-Activated Protein Kinase 3/métabolisme , Mitogen-Activated Protein Kinase Kinases/antagonistes et inhibiteurs , Monocytes/métabolisme , Phosphorylation , Liaison aux protéines , Récepteurs facteur croissance nerf/biosynthèse , Récepteurs aux facteurs de nécrose tumorale/biosynthèse , Transduction du signal , Facteur de nécrose tumorale alpha/biosynthèse , p38 Mitogen-Activated Protein Kinases/antagonistes et inhibiteursRésumé
By searching an EST database, we identified two TNF receptor superfamily members (named mTNFRH1 and mTNFRH2). Amino acid sequences are highly conserved between the two receptors (78% identity). The chromosomal loci of mTnfrh1 and mTnfrh2 genes are found in distal chromosome 7 in the mouse. mTNFRH1 and mTNFRH2 do not contain the cytoplasmic domain, indicating that they might function as decoy receptors. Furthermore, an alternatively spliced form of mTNFRH1 was found which contains neither the transmembrane domain nor the cytoplasmic domain, thus presumably existing as a soluble form. Northern blot analysis showed that mTnfrh1 mRNA was negligibly expressed in tissues, while mTnfrh2 mRNA was strongly expressed in spleen, lung, liver, kidney, and testis. When the extracellular domains of mTNFRH1 and mTNFRH2 were expressed in bacteria, their molecular weight of extracellular region was approximately 15 kDa. Both of the soluble forms were effective in inhibiting T-cell proliferation stimulated by anti-CD3 monoclonal antibody. Our data suggest that mTNFRH1 and mTNFRH2 may be implicated in exerting a modulatory role in the immune response.